ARTICLE | doi:10.20944/preprints202109.0052.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: RNAi; drug delivery; siRNA delivery; DsiRNA delivery; RNAi delivery; Chol-DsiRNA polymer micelles; Chol-siRNA polymer micelles
Online: 3 September 2021 (08:56:48 CEST)
RNA interference (RNAi) molecules have tremendous potential for cancer therapy but are limited by insufficient potency after i.v. administration. We previously found that polymer complexes (polyplexes) formed between 3’-cholesterol-modified siRNA (Chol-siRNA) or DsiRNA (Chol-DsiRNA) and the cationic diblock copolymer PLL-PEG[5K] greatly increase RNAi potency against stably expressed LUC mRNA in primary syngeneic murine breast tumors after daily i.v. dosing. Chol-DsiRNA Polyplexes, however, maintain LUC mRNA suppression ~48 h longer after the final dose than Chol-siRNA Polyplexes, suggesting they are a better candidate formulation. Here, we directly compared the activities of Chol-siRNA and Chol-DsiRNA Polyplexes in primary murine 4T1 breast tumors against STAT3, a therapeutically relevant target gene overexpressed in many solid tumors including breast cancer. We found that Chol-siSTAT3 Polyplexes suppressed STAT3 mRNA in 4T1 tumors with similar potency (half-maximal ED50 0.3 mg/kg) and kinetics over 96 hours as Chol-DsiSTAT3 Polyplexes but with slightly lower activity against total Stat3 protein (29% vs. 42% suppression) and tumor growth (11.5% vs. 8.6% rate-based T/C ratio) after repeated i.v. administration of tumor-saturating doses every other day. Thus, both Chol-siRNA Polyplexes and Chol-DsiRNA Polyplexes may be suitable clinical candidates for RNAi therapy of breast cancer and other solid tumors.
ARTICLE | doi:10.20944/preprints202307.2102.v1
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: Caesarean section; vaginal delivery; nature delivery; Complication
Online: 31 July 2023 (10:44:28 CEST)
We can improve our knowledge of the factors influencing women's decisions to have a caesarean section rather than a vaginal delivery, slow the rise in the caesarean section rate, encourage mothers to have vaginal delivery, and provide practical solutions to health system planners through statistical analysis of the proportion of women who prefer caesarean sections. This investigation is cross-sectional. It involved gathering information from 60 women (20–42 years old) who had given birth via caesarean section over four months, beginning in October 2022 and ending in January 2023. The main reasons of a caesarean section were presence of a fibrous node (caused by previous caesarean sections that were repeated) at 16.67%, intrauterine foetal death at 15%, cervical stenosis at 8.33% , 8.33% of births were repeated due to obstructed labour; 6.66% of caesareans were carried out because the mother contracted or had her uterus removed in order to prevent having children. This study found that there were a lot of complications. The bleeding or anaemia cases accounted for the highest percentage of complications (20%), followed by high blood pressure (16.67%), high fever (10%), and either shortness of breath, blood clotting, urinary tract infection, or wound inflammation (10%). The results of the current study indicated that the level of education, the employment of mothers, and the age of the pregnant were the most important social and demographic factors for increasing the rate of caesarean sections
REVIEW | doi:10.20944/preprints202308.0228.v1
Subject: Engineering, Bioengineering Keywords: Polyethylene glycol; Cellulose; Drug delivery; Vaccine delivery; Hydrogel; Immunogenicity.
Online: 3 August 2023 (02:46:08 CEST)
Due to their distinct physical, chemical, and biological characteristics, biopolymers, in particular Poly Ethylene Glycol (PEG) and Cellulose, are frequently used in biomedical medicine as drug or vaccine delivery systems. In this study, we have done a systematic review and a meta-analysis to compare current developments in many PEG and cellulose-based hydrogels, including double network hydrogels, injectable hydrogels, sliding hydrogels, conductive hydrogels, responsive hydrogels, and nanocomposite hydrogels. The pharmacokinetic properties, including physicochemical properties, biocompatibility, biodegradability, temperature, and pH, have been studied as these critical factors are to be considered for deciding the suitability of the drug for delivery. Moreover, the study has evaluated the controlled-release parameters such as half-life, circulation time, maximum release percentage of loaded drug released, burst release, maximum release, and drug-release kinetics. Finally, the efficacy and immune response of hydrogel was studied for future choice, including the cellulose hydrogel system in COVID-related long-term vaccine delivery. The finding revealed that cellulose-based hydrogel is effective for vaccine delivery.
REVIEW | doi:10.20944/preprints202305.0289.v1
Subject: Chemistry And Materials Science, Nanotechnology Keywords: cancer therapy; nanomedicine; drug delivery; pH-responsiveness; EPR; intratumoral delivery; intracellular delivery; nanoparticles; metal-organic frameworks
Online: 5 May 2023 (03:45:54 CEST)
The paradigm of drug delivery via nano- and microcarriers is one of the leading ideas that enable overcoming the limitations of traditional chemotherapy. The trend toward more complex drug carriers capable of multifunctionality is observed in the literature. To date, prospects of stimuli-responsive systems to control the cargo release in the lesion nidus are widely accepted. Both endogenous and exogenous stimuli are employed for this purpose, however, endogenous pH is one of the most common triggers. Unfortunately, scientists face difficulties in the implementation of this idea since a range of biological barriers, drug bioavailability issues, and challenges in the synthesis of carriers with required properties have arisen. Here, we discuss fundamental strategies of pH-responsive drug delivery as well as limits in its application and reveal the main problems, weak sides, and reasons for poor clinical results. Also, we have made an attempt to formulate the profiles of "ideal" drug carrier in the frame of different strategies and considered recently published studies through the lens of these profiles. This approach enables the identification of current trends and promising vectors in the development of pH-responsive drug delivery systems, as well as challenges to be resolved in the next generation of carriers.
REVIEW | doi:10.20944/preprints201910.0296.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: nasal delivery; glioblastoma multiforme; drug delivery; nanoparticles; nose-to-brain delivery; pre-clinical studies; clinical evaluation
Online: 27 October 2019 (09:36:27 CET)
Glioblastoma (GBM) is the most lethal form of brain tumor, characterized by rapid growth and surrounding tissue invasion. The current standard treatment is surgery followed by radiotherapy, and concurrent chemotherapy, typically with temozolomide. Although extensive research has been performed over the past years to develop an effective therapeutic strategy for the treatment of GBM, efforts have not provided major improvements in the overall survival of patients with GBM. Thus, new therapeutic approaches are urgently needed. A major challenge in the development of therapies for central nervous system (CNS) disorders is overcoming the blood–brain barrier (BBB). In this context, the intranasal (IN) route of drug administration has been proposed as a non-invasive alternative route to directly targeting the CNS. In fact, this route of drug administration may bypass the blood-brain barrier and reduce systemic side effects. Recently, formulations have been developed to further enhance nose-to-brain transport, mainly with the use of nano-sized and nanostructured drug delivery systems. The focus of this review will be on the strategies developed to deliver a number of anticancer compounds for the treatment of GBM using the nasal administration. In particular, the specific properties of nanomedicines proposed for the nose-to-brain delivery will be critically evaluated. The number of preclinical and clinical data reviewed support the idea that nasal delivery of anticancer drugs might represent a breakthrough advancement in the fight against GBM.
REVIEW | doi:10.20944/preprints202311.0246.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: bladder cancer; non-muscle-invasive cancer; local intravesical drug delivery; colloidal drug delivery systems; indwelling devices; sustained delivery
Online: 3 November 2023 (11:26:53 CET)
Treatment of bladder cancer remains a critical unmet need and requires advanced approaches, particularly the development of local drug delivery systems. The physiology of the urinary bladder causes the main difficulties in the local treatment of bladder cancer: regular voiding prevents the maintenance of optimal concentration of the instilled drugs, while poor permeability of the urothelium limits the penetration of the drugs into the bladder wall. Therefore, much research effort is spent to overcome these hurdles, thereby improving the efficacy of available therapies. The explosive development of nanotechnology, polymer science and related fields has contributed to the emergence of a number of nanostructured vehicles (nano- and micro scale) applicable for intravesical drug delivery. Moreover, the engineering approach has facilitated the design of several macro-sized depot systems (centimeter scale) capable of remaining in the bladder for weeks and months. In this article, the main rationales and strategies for improved intravesical delivery are reviewed. Here, we focused on analysis of colloidal nano- and micro-sized drug carriers, and indwelling macro-scale devices which were evaluated for applicability in local therapy of bladder cancer in vivo.
REVIEW | doi:10.20944/preprints202304.0956.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: therapeutic vaccines; mRNA vaccines; antigenic delivery; whole yeast vaccine; delivery vehicle
Online: 26 April 2023 (04:31:14 CEST)
In the last decades, technological advances related to RNA manipulation enabled and expanded its application in vaccine development. This approach comprises synthetic single-stranded mRNA molecules that direct the translation of the antigen responsible for activating the desired immune response. The success of RNA vaccines depends on the delivery vehicle employed. Among the systems, yeasts emerge as a new approach to a natural delivery platform. The presence of β-glucans and mannans in its wall is responsible for the adjuvant action of this system. Yeasts are already employed to deliver protein antigens, with success and efficacy demonstrated through pre-clinical and clinical trials. Yeast β-glucan capsules, microparticles, and nanoparticles are capable of modulating host immune responses and have a high capacity to carry RNA and small molecules, with bioavailability upon oral immunization and with targeting to receptors present in anti-gen-presenting cells (APCs). Besides, yeasts are interesting vehicles for the protection and specific delivery of therapeutic vaccines based on shRNA or dsRNA. In this review, we present an overview of the attributes of yeast or its derivatives for the delivery of RNA-based vaccines, discussing their current challenges and prospects for using this promising strategy.
ARTICLE | doi:10.20944/preprints202310.0922.v1
Online: 16 October 2023 (03:39:25 CEST)
The release of drugs from core/shell nanoparticles (NPs) is a crucial factor in ensuring high re-producibility, stability, and quality control. It serves as the scientific basis for the development of nanocarriers. Several factors, such as composition, composition ratio, ingredient interactions, and preparation methods, influence the drug release from these carrier systems. The objective of our study was to investigate and discuss the relationship between modifications of core/shell NPs as multifunctional drug delivery systems and the properties and kinetics of drug release using an in vitro drug release model. In this paper, we prepared four core/shell NPs consisting of a super-paramagnetic iron oxide NPs (Fe3-δO4) core encapsulated by a biocompatible thermo-responsive copolymer, poly(2-(2-methoxy) ethyl methacrylate-oligo (ethylene glycol) methacrylate) or P(MEO2MAx-OEGMA100-x) (where x and 100-x represent the molar fractions of MEO2MA and OEGMA, respectively), and loaded with doxorubicin (DOX). Colloidal behavior measurements in water and PBS as a function of temperature showed an optimization of the lower critical solu-tion temperature (LCST) depending on the molar fractions of MEO2MA and OEGMA used to form each NPs. In vitro studies of doxorubicin release as a function of temperature demonstrated a high control of release based on the LCST. A temperature of approximately 45°C for 60 h was sufficient to release 100 % of the DOX loaded in the NPs for each sample. In conclusion, external stimuli can be used to modulate the drug release behavior. Core/shell NPs hold great promise as a technique for multifunctional drug delivery systems.
REVIEW | doi:10.20944/preprints202103.0303.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: Fungi; Bacteria; Holobionts; Delivery
Online: 11 March 2021 (10:12:39 CET)
Abstract Bacteria and fungi are both used in biological seed treatments. While all have potential uses, some organisms are more widely and successfully used than others. Shelf life is an important consideration. For this reason, organisms that lack cell walls are more difficult to use than ones with long-lasting spores. Bacillus and Trichoderma are both widely effective, have good shelf life, and are frequently used. However, Rhizobiacae lack cell walls, which is a limitation; they are widely used because their symbiosis with legumes facilitates nitrogen fixation which is an important factor that provides economic, agricultural and environmental sustainability. For all organisms, proper formulation is critical for success; this is especially true for Rhizobiacae and other gram-negative bacteria. There are several specialized processes to deliver microbial agents or to enhance their biological activity, such as solid matrix priming and hydroseeding. Biorational chemicals derived from microorganisms are also frequently used. Both living organisms and biorationals provide benefits to plant agriculture. They can control diseases and increase resistance to abiotic stresses such as drought, temperature, salt, and flooding. They also can enhance mineral nutrition and photosynthesis. For these applications, the most effective ones colonize roots internally and provide season-long benefits. These endophytes induce systemic changes in plants’ gene expression and encoding of proteins.
ARTICLE | doi:10.20944/preprints202306.1941.v1
Subject: Computer Science And Mathematics, Computer Networks And Communications Keywords: metaverse; multiuser ivrtual environments; experience delivery network; content delivery network; cloud edge
Online: 28 June 2023 (03:52:54 CEST)
In the trend of transforming existing systems and services into non-face-to-face models, the concert industry is also showing movements toward transitioning to virtual formats. Physical concerts in the real world require venues that can accommodate hundreds to tens of thousands of spectators, but non-face-to-face methods that can accommodate large audiences face various limitations. Moreover, to elevate the satisfaction level of virtual concert attendees to that of real-world concerts, it's important to implement interaction between performers and audiences. Modern metaverse platforms apply cutting-edge network technologies to accommodate numerous users within a single channel. Many researchers are adopting network technologies such as SDN (Software Defined Networking) and CDN (Content Delivery Network) to set up a virtual concert that can accommodate large audiences. In this paper, we propose a network framework to be designed for the composition of virtual concerts. In particular, we separate a channel dedicated to interaction in order to provide an immersive experience of exchanging interactions between performers and audiences. As massive audiences transmitting interaction data to the performer in a 1:N format can lead to problems with acceptance and latency, this study introduces a concept of a channel form called 'Zone' and proposes an interaction data channel network framework that does not compromise immersion. The proposed framework supports tasks for effectively transmitting interaction data using network technologies for metaverse platforms like XDN and clustering algorithms like fuzzy c-means. We also suggest a CDN-based architecture that can ensure low latency for performers to transmit interaction data to the audience.
ARTICLE | doi:10.20944/preprints202308.1338.v1
Subject: Computer Science And Mathematics, Mathematical And Computational Biology Keywords: drug delivery; bayes; diffusion equation
Online: 18 August 2023 (07:42:10 CEST)
The paradigm of molecular communications is applied to the concrete case for delivering electrically charged nanoparticles to tumor. Once them have been injecetd in blood it is expecetd an optimal outcome as to reduce toxicity and minimal dispersion of drugs in the blood stream. With a fraction of nanoparticles arrives to surface of tumor, the scattered part of injected ones can minimize the success of scheme of drug delivery. In this paper is presented a theory based at the sequence electrodynamics-diffusion-Bayes theorem. The resulting probability of Bayes at the end of sequence, might be telling us that dynamical processes based in the injection of electrically charged nanoparticles might be dictated by stochastic formalism more that biochemical approaches by which makes impossible to know the success or fail of drug delivery dynamics. Illustrations demonstrating the transition of a linear to nonlinear scenario are presented
REVIEW | doi:10.20944/preprints202306.1009.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: Antifungal; Drug delivery; Polymers; Nanometer
Online: 14 June 2023 (07:57:36 CEST)
Nanosystems-based antifungal agents have emerged as an effective strategy to address issues related to drug resistance, drug release, and toxicity. Among the different materials used for drug delivery, multifunctional polymers have proven to be ideal due to their versatility. This review provides an overview of the various types of nanoparticles used in antifungal drug delivery systems, with a particular emphasis on the types of polymers used. The review focuses on the application of drug delivery systems and the release behavior of these systems. Furthermore, the review summa-rizes the critical physical properties and relevant information utilized in antifungal polymer nanomedicine delivery systems, and briefly discusses the application prospects of these systems.
ARTICLE | doi:10.20944/preprints202305.1243.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: Vaccine; Antigen-delivery; ZIKV; Yeast
Online: 17 May 2023 (11:00:56 CEST)
Improving antigen presentation is crucial for the success of immunization strategies. Yeasts are classically used as biofactories to produce recombinant proteins and are efficient vehicles for the delivery of vaccine antigens, besides present adjuvants properties. Despite the absence of epidemic outbreaks, several vaccine approaches continue to be developed for Zika virus infection. These prophylactic strategies are fundamental given the severity of clinical manifestations, mainly due to viral neurotropism. The present study aimed to evaluate in vivo the immune response induced by P. pastoris recombinant strains displaying epitopes of the Envelope (ENV) and NS1 ZIKV proteins. Intramuscular immunization with heat-attenuated yeast enhanced the secretion of IL-6, TNF-α, and IFN-γ, besides activation of CD4+ and CD8+ T cells, in BALB/c mice. P. pastoris displaying ENV epitopes induced a more robust immune response, increasing immunoglobulin production, especially IgG isotypes. Both proposed vaccines showed the potential to induce immune responses without adverse effects, confirming the safety of administering P. pastoris as a vaccine vehicle. Here we demonstrated, for the first time, the evaluation of a vaccine against ZIKV based on a multiepitope construct, using yeast as a vehicle, reinforcing the applicability of P. pastoris as a whole yeast cell vaccine.
REVIEW | doi:10.20944/preprints202112.0315.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: Nanotechnology; Niosomes; Targeted Drug Delivery
Online: 20 December 2021 (14:18:53 CET)
Nanotechnology is making significant transformation to our world, especially in healthcare and the treatment of diseases. It is widely used in different medical applications, such as in treatment and detection. Targeting diseased cell with nanomedicines is one of the numerous applications of nanotechnology. Targeted drug delivery systems for delivering various types of drugs to specific sites are such a dynamic area in pharmaceutical biotechnology and nanotechnology. Compared to conventional drugs, nanomedicines have a higher absorption and bioavailability rate, improving efficacy and minimizing side effects. There are several drug delivery systems including metallic nanoparticles, polymers, liposomes, and microspheres, but one of the most important is the niosomes, which are produced by nonionic surfactants. Because of the amphiphilic nature and structure, hydrophilic or hydrophobic drugs can be loaded into niosome structures. Other compounds, including cholesterol, can also be applied to the niosomes' backbone to rigidize the structure. Several variables such as the type of surfactant in niosome production, the preparation method, and the hydration temperature can affect the structure of the niosomes. Nevertheless, in-silico design of drug delivery formulations requires molecular dynamic simulation tools, molecular docking, and ADME (absorption; distribution; excretion; metabolism) properties, which evaluate physicochemical features of formulation and ADME attitudes before synthesis, investigating the interaction between nano-carriers and specific targets. Hence, experimenting in-vitro and in-vivo is essential. In this review, the basic aspects of niosomes are described including their structure, characterization, preparation methods, optimization with in-silico tools, factors affecting their formation, and limitations.
REVIEW | doi:10.20944/preprints202212.0112.v1
Subject: Chemistry And Materials Science, Nanotechnology Keywords: Gastro retentive drug delivery systems; non-effervescent systems; floating drug delivery systems; microballoons; CRDDS
Online: 7 December 2022 (02:26:58 CET)
Gastro-retentive floating microspheres were developed as a result of the recent advancements in floating delivery systems for drugs (FDDS), which included the uniform dispersion of multiparticulate dosage forms along the GIT. This could lead to more consistent drug absorption and a lower risk of local irritation. Microballoons (MB), a multi-unit extended release with a sphere-shaped cavity encased in a tough polymer shell, have been developed as a dosage form with exceptional buoyancy in the stomach. This preparation for constrained intestinal absorption is made to float on top of gastric acid, that has a relative density lower than 1.By using enteric acrylic polymers and the emulsion solvent diffusion method, microballoons are prepared and filled to drug in one‘s outer polymer casings. Enteric acrylic plastics are used to generate microballoons that are drug-loaded in one‘s external polymer casings and dissipate in a solution of dichloromethane and ethanol. Cavity development in microparticles seems to be particularly correlated with dichloromethane evaporation. Microballoons with a drug distributed or dispersed all through the particle-matrix have the potential for a controlled drug release and float continuously for more than 12 hours in vitro out over the surface of an acidified dissolution medium with surfactant. The drug is released slowly and at the desired rate as the microballoons glide over the components of the stomach, increasing gastro-retention time and lowering fluctuations in plasma concentration.
REVIEW | doi:10.20944/preprints202311.1890.v1
Subject: Medicine And Pharmacology, Pharmacy Keywords: clays; color cosmetics; efficacy; delivery; formulation
Online: 30 November 2023 (05:25:25 CET)
The use of clays in beauty care comes from ancient times, with therapeutic use since prehistory, and it is considerably relevant in the current cosmetic industry worldwide. In our review, we described types of clay and clay minerals used in cosmetics and dermocosmetics, compositions, usages as active compounds and excipients, and observations about formulation techniques. From this research, we could notice that although many scientific and specialized literature reported the characterization of clays, only some involving efficacy tests when incorporated into cosmetic products, mainly concerning haircare applications. By the exposed, our review could be considered and encouraged in the coming years to provide scientific and technical information for the cosmetic industry regarding the multifunctional use of clays and clay minerals.
ARTICLE | doi:10.20944/preprints202310.0609.v1
Subject: Medicine And Pharmacology, Emergency Medicine Keywords: cancer treatments; nanotechnology; nanoparticles; drug delivery.
Online: 10 October 2023 (08:37:52 CEST)
Cancer is among the leading causes of death worldwide. Therefore, timely diagnosis and appropriate treatment are very important. There are many disadvantages that come with traditional cancer treatments, such as chemotherapy and radiotherapy. In these treatments, the specific drug concentration affects not only the tumor site but also healthy tissues or organs. One of the foremost promising uses of nanotechnology is in the field of medical technology and specific site targeting can be achieved due to manipulation of materials at a nanometric scale. Nanotechnology offers specific benefits in terms of cancer therapy by enhancing it and reducing its adverse effects by guiding drugs to selectively target cancer cells. In addition, the use of minute amounts of medicine can lead to cost savings. Furthermore, nanoparticles can also be used as imaging agents to improve cancer diagnostics, therapeutics, and treatment management. Thus, this review has focused on the different types of nanoparticles used in cancer therapy, their action mechanisms, and their benefits and applications in diagnosis, imaging, and treatment. This review sums up the parameters that need to be considered when designing systems for cancer therapy while considering the desired characteristics of the nanoparticles from the biological point of view.
REVIEW | doi:10.20944/preprints202309.0343.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: skin cancer; drug delivery; natural products
Online: 6 September 2023 (05:04:49 CEST)
Skin cancer is a disease that reflects most malignant neoplasms worldwide, whose rate of involvement has increased significantly in recent decades. Treatments that offer efficient results with attenuation of adverse reactions and greater patient compliance have been the subject of many systematic investigations. This review aims to qualitatively present published works that showed new strategies to increase the penetration power of natural substances through the skin in the topical treatment against skin cancer. In this sense, nanoengineering mechanisms, the iontophoresis technique, and photodynamic therapy using natural products (NP) contribute to new knowledge about substance carrier strategies in topical treatments against skin cancer.
ARTICLE | doi:10.20944/preprints202306.1278.v1
Subject: Engineering, Architecture, Building And Construction Keywords: Delivery; Housing; Projects; Roles; Stakeholders; Sustainability
Online: 19 June 2023 (03:59:46 CEST)
The role stakeholders play is fundamental to the realisation of sustainable development. Con-sequentially, there is need for the major stakeholders to be fully aware of their respective roles. Thus, this paper focused on assessing the Stakeholders roles in sustainable housing projects in Lagos State, Nigeria. Structured questionnaire survey was used to collect data from 259 stake-holders involved in sustainable housing projects in Lagos State, Nigeria. A total of 203 responses were obtained, representing 78% response rate. Primary data regarding the extent of stakeholders awareness of their roles in sustainable housing were collected. The data collected were analysed using mean ranking analysis and analysis of variance (ANOVA). The data collected were used to determine the extent of awareness of the stakeholders’ role in sustainable housing pro-jects in Lagos State, Nigeria. The results showed that all the stakeholders were aware of their respective roles in the delivery of sustainable housing projects and were highly conscious of them. Although their extent of awareness was at varying levels, there was no statistically significant difference of opinions amongst the different categories of stakeholders in the delivery of sustainable housing projects. The study concluded that Government and Project Managers have key roles to play as major stakeholders in the delivery of sustainable housing projects. The knowledge of the awareness of stakeholders’ roles in the delivery of sustainable housing project provides invaluable information to stakeholders regarding the important roles to focus attention on in achieving sustainable housing projects. The study provides a veritable basis for assessment of sustainable housing project in Lagos State, Nigeria.
ARTICLE | doi:10.20944/preprints202108.0458.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Hyaluronan; nanogels; ocular delivery; permeation enhancer
Online: 23 August 2021 (15:08:12 CEST)
The anatomy and physiology of the eye strongly limit the bioavailability of locally administered drugs. The entrapment of therapeutics into nanocarriers represents an effective strategy to topically treat some ocular disorders, as they may protect the entrapped molecules, facilitating drug residence on the ocular surface and/or its penetration into different ocular compartments. The present work shows the activity of hyaluronan-cholesterol nanogels (NHs) as ocular permeation enhancers. Thanks to their bioadhesive properties, NHs firmly interact with the superficial corneal epithelium, without penetrating the stroma, modifying the transcorneal penetration of loaded therapeutics. Ex-vivo transcorneal permeation experiments showed that the permeation of hydrophilic drugs (i.e. tobramycin and diclofenac sodium salt), loaded in NHs, is significantly enhanced when compared to the free drug solutions. On the other side the permeation of hydrophobic drugs (i.e. dexamethasone and piroxicam) is strongly dependent on the water solubility of the entrapped molecules. The obtained results suggest that NHs formulations can improve the ocular bioavailability of the instilled drugs by increasing their preocular retention time (hydrophobic drugs) or facilitating their permeation (hydrophilic drugs), thus opening the route for the application of HA-based NHs in the treatment of both anterior and posterior eye segment diseases.
ARTICLE | doi:10.20944/preprints202106.0273.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Men; Urban; HIV self-testing; Delivery
Online: 9 June 2021 (22:14:21 CEST)
Background: HIV self-testing (HIVST) is one of the recommended approaches for HIV testing services, particularly for helping reach populations who would not normally access facility-based HIV testing. HIVST must be tailored to different populations to ensure uptake. Objective: The main objective of this study was to develop an acceptable HIVST delivery strategy to help improve urban men’s engagement with HIV services. Methods: We invited key stakeholders for urban men’s HIV services to participate in a co-creation workshop aimed at developing HIVST delivery approaches for urban men, using eThekwini municipality as a study setting. We conducted purposive sampling to include health care users and health care providers, representing a range of views across the public sector and voluntary sector. We employed the Nominal Group Technique (NGT) method for data collection. The NGT workshop was conducted in two consecutive phases: phase one was focused on determining barriers for men’s engagement with the current/facility-based HIV testing services; phase two was aimed at determining HIVST delivery strategies. We used the results of the NGT to design a tailored HIVST strategy for urban men in eThekwini District. Results: Participants identified the following psychological factors as the most important barriers to uptake of HIV testing services by urban men: stigma, ignorance about the importance of testing and testing process as well as fear of positive test results. Key stakeholders suggested internal motivation strategies as a potentially effective approach to support HIVST delivery strategy. Guided by the NGT results, we designed a HIVST delivery strategy that is supported by a risk communication approach Conclusion: We designed an evidence-based risk communication mobile health (mHealth) strategy coupled with SARS COV-2 self-testing tailored to improve men’s uptake of HIVST. A follow-up study to evaluate the feasibility of implementing these approaches is recommended.
REVIEW | doi:10.20944/preprints202309.1793.v1
Subject: Biology And Life Sciences, Neuroscience And Neurology Keywords: neurodegenerative disorders; blood-brain barrier; non-invasive delivery; device-related delivery; Alzheimer’s; Parkinson’s; ALS; Down Syndrome
Online: 27 September 2023 (04:19:06 CEST)
Device-mediated, non-invasive drug delivery across the blood-brain barrier (BBB) represents a significant advancement in treating neurological diseases. The BBB is a tightly packed layer of endothelial cells that shields the brain from harmful substances in the blood, allowing necessary nutrients to pass through. It is a highly selective barrier, which poses a challenge to delivering therapeutic agents into the brain. Several non-invasive techniques and devices have been proposed or investigated to enhance drug delivery across the BBB. This paper presents the current state of the art and case studies that address the pharmacology, technology, delivery systems, regulatory approval, ethical concerns, and future possibilities.
ARTICLE | doi:10.20944/preprints202308.1047.v1
Subject: Medicine And Pharmacology, Ophthalmology Keywords: Age-related Macular Degeneration (AMD); Cornea; docosahexaenoic acid (DHA); drug delivery; non-invasive ocular delivery platform (NIODP); ocular disease; omega-3; retina; retinal delivery; retinal dis
Online: 14 August 2023 (15:18:22 CEST)
To this day, use of oily eye drops and non-invasive retinal delivery remains a major challenge. Oily eye drops usually cause ocular irritation and interfere with normal function of the eye, while ocular injections for retinal drug delivery cause significant adverse effects and a high burden on the healthcare system. Here the authors report a novel topical Non-Invasive Ocular Delivery Platform (NIODP) through the periorbital skin for high efficiency anterior and posterior ocular delivery in a non-human primate model (NHP). A single dose of about 7mg JV-MD2 (omega-3 DHA) via the NIODP reached the retina at Cmax of 111µg/g and the cornea at Cmax of 66µg/g. NIODP also delivered JV-DE1, an anti-inflammatory agent in development for dry eye diseases, as efficiently as eye drops did to anterior segments of NHP. The topical NIODP seems to transport drug candidates through the cornea pathway to the anterior and via the conjunctiva/sclera pathway to the posterior segments of the eye. The novel NIODP method has the potential to reshape the landscape of ocular drug delivery, especially for oily eye drops and retinal delivery, where the success of treatment lies in the ocular tolerability and bioavailability of drugs in the target tissue.
REVIEW | doi:10.20944/preprints202201.0372.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: gene therapy; non-viral vectors; gene delivery; cancer; nucleic acid delivery; nanoparticles; lipids; lipid nanoparticles; mRNA; siRNA
Online: 25 January 2022 (09:01:41 CET)
The research and development of non-viral gene therapy has been extensive over the past decade and has received a big push thanks to the successful approval of non-viral gene therapy products in recent times. Despite these developments, gene therapy applications in cancer have been limited. One of the main causes of this has been the imbalance in development of delivery vectors as compared to nucleic acid payloads. This paper reviews non-viral vectors that can be used to deliver nucleic acids for cancer treatment. It discusses various types of vectors and highlights their current applications. Additionally, it also discusses perspective on regulatory landscape to facilitate commercial translation of gene therapy.
REVIEW | doi:10.20944/preprints202103.0342.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: glioblastoma; high-grade glioma; refractory glioma; direct delivery; convection enhanced delivery; neuro-oncology; refractory glioblastoma; clinical trials
Online: 12 March 2021 (15:01:51 CET)
Development of effective treatments for high-grade glioma (HGG) is hampered by 1) the blood-brain barrier (BBB), 2) an infiltrative growth pattern, 3) rapid development of therapeutic resistance, and, in many cases, 4) dose-limiting toxicity due to systemic exposure. Convec-tion-enhanced delivery (CED) has the potential to significantly limit systemic toxicity and in-crease therapeutic index by directly delivering homogenous drug concentrations to the site of disease. In this review, we present clinical experiences and preclinical developments of CED in the setting of high-grade gliomas.
ARTICLE | doi:10.20944/preprints201812.0249.v1
Subject: Engineering, Energy And Fuel Technology Keywords: Grocery Delivery, Energy-Savings, CO2-Savings, Munich, Break-Even Point, Electric Delivery Vehicle, Customer Pickup, Modal Shift
Online: 20 December 2018 (12:46:13 CET)
TThe number of supermarkets offering a grocery delivery has been increasing during the last years. Many studies deduce CO2 emission savings using this concept. Since the delivery of groceries also consumes energy and produces emissions, break-even points can be calculated, from where the delivery has environmental advantages compared to the customer pickup. In this paper, influences of differing vehicle use on break-even points for savings of energy and CO2 emissions are analyzed for the case of Haidhausen Süd, a city district of Munich in Germany. Internal combustion engine and electric vehicles are investigated to depict current as well as future trends. After an introduction to the used methodology, the potential to save energy and CO2 emissions related to the delivery of groceries in the chosen district of Munich is evaluated. Afterwards, influences on the break even points are presented and discussed. As the results show, a delivery of groceries leads to energy and carbon dioxide savings in a wide range of private vehicle use for grocery shopping trips. Nevertheless, if the complete customer vehicle fleet is electrified, the use of delivery vehicles with an internal combustion engine can cause an additional environmental impact at the current modal split for shopping trips in Germany.
REVIEW | doi:10.20944/preprints202312.0041.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: Cardiovascular disease (CVD); biomedicine; nanotechnology; drug delivery
Online: 1 December 2023 (08:10:55 CET)
Cardiovascular disease (CVD) accounts for nearly one-third of all global fatalities, establishing itself as a leading cause of death. To address this pressing issue, there is a growing demand for improved diagnostic methods and secure, non-invasive imaging techniques that can deliver precise insights into the progression of CVD. The success of personalized therapy for CVD depends on a couple of critical factors: accurate diagnosis and early detection. Therapeutic options for conditions like CVD, which develop over several decades, are highly specific to the individual's condition and the stage of the disease. In the field of biomedicine, nanotechnology has become increasingly prominent as a tool with diverse applications, including diagnostics, biosensing, and drug delivery. This review article offers an in-depth look at the most recent developments in the utilization of nanotechnology for detecting and managing prevalent cardiovascular diseases, providing valuable insights into this crucial area of healthcare research.
ARTICLE | doi:10.20944/preprints202311.1167.v1
Subject: Medicine And Pharmacology, Pharmacy Keywords: Nanoparticles; chitosan; osteomyelitis, drug delivery; antimicrobials; gentamicin.
Online: 17 November 2023 (12:57:47 CET)
Chitosan nanoparticle delivery systems have potential for enhancing bone healing and addressing osteomyelitis. The objective was to deliver antimicrobial agents capable of preventing or treating osteomyelitis. Each formulation was optimized to achieve desired characteristics in terms of size (ranging from 100 to 400 nm), PDI (less than 0.5), zeta potential (typically negative), and in vitro release profiles for gentamicin. Entrapment percentages varied with gentamicin ranging from 10% to 65%. The chitosan nanoparticles exhibited substantial antimicrobial efficacy, particularly against both P. aeruginosa and MRSA, with zones of inhibition ranging from 13 to 24 mm and complete reduction in colony forming units observed between 3 to 24 hours. These chitosan nanoparticle formulations loaded with antimicrobials hold promise for addressing orthopedic complications.
REVIEW | doi:10.20944/preprints202307.1827.v2
Subject: Engineering, Bioengineering Keywords: biopolymers; nanomaterials; drug delivery systems; proteins; polysaccharides
Online: 18 October 2023 (05:16:06 CEST)
Encapsulated nanofibers have emerged as a promising approach for the treatment of acne, owing to their ability to provide controlled release, targeted delivery, increased efficacy, and improved stability. Electrospinning is a well-established method for producing encapsulated nanofibers and has been shown to be effective for encapsulating various active ingredients. However, there are still several challenges that need to be addressed in the development of encapsulated nanofibers for acne treatment. One major challenge is the need for comprehensive in vitro and in vivo studies to evaluate the safety and efficacy of these treatments. The cost and scalability of production also need to be considered to make these treatments accessible and affordable for patients. In addition, the long-term stability of encapsulated active ingredients is another challenge in the development of encapsulated nanofibers for acne treatment. Regulatory frameworks need to be developed to ensure the safety and efficacy of these treatments. Future research may focus on developing multifunctional nanofibers that combine active ingredients with other properties, such as antimicrobial, anti-inflammatory, and wound-healing properties, to provide a comprehensive approach to acne treatment. Moreover, the development of nanofiber-based skincare products may have a significant impact on the cosmetic industry. Overall, while there are still challenges to overcome, the potential benefits of encapsulated nanofibers for acne treatment make them an exciting and promising area of research for the future. In particular, the integration of smart drug delivery systems and responsive materials may enable the development of more personalized and effective treatments for acne. The development of new materials and encapsulation techniques, as well as the exploration of combination therapies that target multiple aspects of acne pathogenesis, are also future perspectives for encapsulated nanofibers in acne treatment.
ARTICLE | doi:10.20944/preprints202306.1882.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: Breast Cancer; Curcumin; Copolymer; Drug delivery; Nanoinformatics
Online: 27 June 2023 (10:23:03 CEST)
Curcumin (CUR) is a phytochemical with potent anticancer activities as demonstrated by both preclinical and clinical studies. CUR bioformulations, including loading in biodegradable polymers, have been explored to increase CUR’s solubility and chemical stability, control its release, and improve its delivery to cancer cells. In this study, copolymers comprising poly (L-lactide)-poly (ethylene glycol)-poly (L-lactide) (PLA-PEG-PLA) and poly (ethylene glycol)-poly (L-lactide)-poly (ethylene glycol) (PEG-PLA-PEG) were designed and synthesized to assess and compare their curcumin delivery capacity and inhibitory potency on MCF-7 breast cancer cells. Molecular dynamics simulations indicated that PLA-PEG-PLA has a higher propensity to interact with the cell membrane and more negative free energy, suggesting it is the better carrier for cell membrane penetration. Our characterization indicated that the microsphere copolymers were synthesized successfully. Of the two formulations, PLA-PEG-PLA experimentally exhibited better results, with an initial burst release of 17.5%, followed by a slow, constant release of the encapsulated drug up to 80%. PLA-PEG-PLA-curcumin showed a significant increase in cell death in MCF-7 cancer cells (IC50 = 23.01 ± 0.85 µM) based on the MTT assay. These data were consistent with gene expression studies of Bax, Bcl2, and hTERT which showed that PLA-PEG-PLA-CUR induced apoptosis more efficiently in these cells. Our study integrates in vitro and in silico approaches to identify an optimal co-polymer for the delivery of CUR to cancer cells.
REVIEW | doi:10.20944/preprints202305.0601.v1
Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: sepsis; diagnostic; treatment; drug delivery; nanomedicine; nanotechnology
Online: 9 May 2023 (08:27:02 CEST)
Sepsis is a life-threatening condition caused by a dysregulated host response to an invading pathogen such as multidrug-resistant bacteria. Despite recent advancements, sepsis is a leading cause of morbidity and mortality, resulting in a significant global impact and burden. This condition affects all age groups, with clinical outcomes depending mainly on timely diagnosis and appropriate early therapeutic intervention. Because of the unique features of nanosized systems, there is a growing interest in developing and designing novel solutions. Nanoscale-engineered materials allow a targeted and controlled release of bioactive agents, resulting in improved efficacy with minimal side effects. Additionally, nanoparticle-based sensors provide a quicker and more reliable alternative to conventional diagnostic methods for identifying infection and organ dysfunction. Despite recent advancements, fundamental nanotechnology principles are often presented in technical formats that presuppose advanced chemistry, physics, and engineering knowledge. Consequently, clinicians may not grasp the underlying science, hindering interdisciplinary collaborations and successful translation from bench to bedside. In this review, we abridge some of the most recent and most promising nanotechnology-based solutions for sepsis diagnosis and management using an intelligible format to stimulate a seamless collaboration between engineers, scientists, and clinicians.
ARTICLE | doi:10.20944/preprints202207.0023.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: electrospinning; morphology structures; propolis; polycaprolactone; drug delivery
Online: 1 July 2022 (17:39:00 CEST)
The structure of wound dressing materials presents one of the most relevant characteristics for effective skin tissue repair. Electrospinning is a common technique used to produce polymeric fibres that can mimic fibrillar disposition of skin extracellular matrix, favouring cell migration, and thus regeneration of the damaged tissue. Moreover, beads, also known as by-products of electrospinning, have potential as reservoirs for sustained drug release. Processing parameters, such as molecular weight and viscosity of the polymer solution, can affect the desirable morphologies of electrospun films. Thereby, this work had the purpose of producing and characterized electrospun polycaprolactone (PCL) mats loaded with propolis, a popular extract in traditional medicine with potential for skin repair aid. Films with different morphologies were obtained depending on the storage period of the solution prior to the lectrospinning, probably due to the PCL hydrolysis. FTIR analyses of the extract confirmed propolis composition. GPC and viscosity analyses demonstrated that the decrease in molar mass over the storage period was responsible for nanostructure diversity. Propolis acts as a lubricant agent, affecting the spun solutions' viscosity and the thermal properties and hydrophilicity of the films. All films are within the value range of the water vapour transpiration rate of the commercial products. The presence of beads did not affect the propolis release pattern. However, "in vitro" wound healing assay showed that propolis-loaded films composed by beaded fibres increased the cell migration process. Thus, it can be inferred that these films presented the potential for wound dressing application.
ARTICLE | doi:10.20944/preprints202112.0246.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: CRISPR; LNP; formulation; NHEJ; HDR; AF4; delivery
Online: 14 December 2021 (18:24:56 CET)
The CRISPR-Cas9 system is an emerging therapeutic tool with the potential to correct diverse ge-netic disorders. However, for gene therapy applications an efficient delivery vehicle is required, capable of delivering the CRISPR-Cas9 components into the cytosol of the intended target cell population. Once there, the ribonucleoprotein complex (RNP) can be transported into the nucleus. Lipid nanoparticles (LNP) serve as promising candidates for delivery of CRISPR-Cas9 RNP. These delivery vehicles have been optimized for the delivery of nucleic acids, such as mRNA. Co-delivery of Cas9 encoding mRNA with the accompanying sgRNA leads to translation of the Cas9 protein and formation of the Cas9 RNP inside the cell. Only recently, direct delivery of the CRISPR-Cas9 RNP complexes has been explored, which requires adjustments to the LNP formulation. In this study, the importance of buffer composition and cationic charge during RNP and ssDNA en-trapment in LNP are demonstrated. After optimizing several formulation parameters, LNP were prepared that were colloidally stable in human plasma and efficiently deliver the SpCas9 RNP and ssDNA for HDR-correction in reporter cells. Under optimal formulation conditions, gene knock-out and gene correction efficiencies as high as 80% and 20%, respectively were achieved at nanomolar CRISPR-Cas9 RNP concentrations.
REVIEW | doi:10.20944/preprints202107.0384.v2
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: miRNAs; valvular heart diseases; aortic stenosis; calcification; mitral valve prolapse, aortic valve defect; vectors; delivery systems; nanoparticles
Online: 8 November 2021 (14:25:40 CET)
miRNAs have recently attracted investigators' interest as regulators of valvular diseases pathogenesis, diagnostic biomarkers, and therapeutical targets. Evidence from in-vivo and in-vitro studies demonstrated stimulatory or inhibitory roles in mitral valve prolapse development, aortic leaflet fusion, and calcification pathways, specifically osteoblastic differentiation and transcription factors modulation. Tissue expression assessment and comparison between physiological and pathological phenotypes of different disease entities, including mitral valve prolapse and mitral chordae tendineae rupture, emerged as the best strategies to address miRNAs over or under-representation and thus, their impact on pathogeneses. In this review, we discuss the fundamental intra- and intercellular signals regulated by miRNAs leading to defects in mitral and aortic valves, congenital heart diseases, and the possible therapeutic strategies targeting them. These miRNAs inhibitors comprise of antisense oligonucleotides and sponge vectors. The miRNA mimics, miRNA expression vectors, and small molecules are instead possible practical strategies to increase specific miRNA activity. Advantages and technical limitations of these new drugs, including instability and complex pharmacokinetics, are also presented. Novel delivery strategies, such as nanoparticles and liposomes, are described to improve knowledge on future personalized treatment directions.
REVIEW | doi:10.20944/preprints202106.0619.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Natural products; Madagascan active principles; Nano-delivery.
Online: 25 June 2021 (12:02:28 CEST)
Natural products endowed of biological activity represent a primary source of commodities ranging from nutrition to therapeutic agents, as well as cosmetic tools, and recreational principles. These natural means have been used by mankind since centuries if not millennia. They are commonly used all over the world and socio-economical contexts but are particularly attractive in disadvantaged area or economically emerging situations all over the world. This is very likely due to the relatively easy recovery of these bioactive principles from the environment, to the low if any cost as well as ease of administration and to the general popular compliance concerning their consumption/ingestion. In this concise review, we focus on some popular bioactive principles of botanical origin which find a wide use in the Madagascan populations. But, due to space limitations only some most common and largely diffused principles in this country are considered. Finally, a possible nanotechnological administration is discussed in the case where a potential therapeutic usage is envisaged.
REVIEW | doi:10.20944/preprints202105.0726.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Artificial Intelligence; Drug Delivery; Cancer; Nanomedicines; Therapeutic
Online: 31 May 2021 (09:59:30 CEST)
Artificial Intellignece (AI) is a platform lending immense assistance in discovering and developing drugs and thus, various such approaches have been developed with the intent of simplifying and improving biomedical operations such as drug repurposing and drug discovery. In the past decade, AI-based investigation of nanomedicines, as well as non-nanomedicines has reached the clinical level. In semblance with the traditional methods of therapy, nanomedicine therapy is employed at limited doses. The study of a variety of drugs resulted in the conclusion that the effect of each drug is variable for every patient and, evaluating that perfect drug combination manually is a time-consuming as well as an inefficient treatment method. Therefore, the use of AI simplifies and reduces the time consumption in determining the perfect customized drug combination for nano-therapy. The area with the most potential for meeting this reality is to optimize the drug and dosage parameters. It is a universally known fact that cancer is dangerous and unique because of the exacting challenges it poses during treatment and, to achieve a better treatment, the therapeutic effect on each patient must be delineated even if the volume of data generated is massive. The article aims at analyzing the AI technologies that help yield results much quicker, make the analyses simple, and efficient.
REVIEW | doi:10.20944/preprints202105.0643.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Nanocarriers; Nanotheranostics; Nuclear Medicine; Nanoparticles; Drug delivery
Online: 26 May 2021 (14:00:58 CEST)
Background: Convectional methods for drug delivery often faces setbacks due to systemic distribution, short half-life and degradation of therapeutics and therefore reduce concentrations of drug available to target tissue. Nanotheranostic provide a novel method for treating and diagnosing diseases Methodology: collection and review of relevant literatureResult: while nanotheranostic offer advantage of personalized medicine and often combines diagnosis and therapy using single molecular approach, nuclear medicine relies on radioactive isotopes to diagnosed and destroys cancer cells. In both cases, nanocarriers such as lipid-based, polymer-based, drug-conjugate, inorganic nanoparticles are used to deliver drugs/probes/isotopes to target site, generating images and thereafter chemotherapy/radiotherapy begins.Conclusion: Nanotheranostic plays important role in diseases diagnostic, therapy, imaging, monitoring of disease progression / response through the use of nanocarriers. This is made possible through nanoparticles/nanocarriers that delivers drug to the target tissues/cells.
ARTICLE | doi:10.20944/preprints202105.0229.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: extracellular vesicles; melanoma; doxorubicin; drug delivery systems.
Online: 11 May 2021 (10:19:50 CEST)
Tailoring extracellular vesicles (EVs) as targeted drug delivery systems to enhance the therapeutic efficacy showed superior advantage over liposomal therapies. Herein, we developed a novel nanotool for targeting B16.F10 murine melanoma, based on EVs stabilized with Polyethylene glycol (PEG) and loaded with doxorubicin (DOX). Nanosized EVs were efficiently enriched from melanoma cells cultured under metabolic stress by ultrafiltration coupled with size exclusion chromatography (UF-SEC) and characterized by size, morphology, and proteome. To reduce their clearance in vivo, EVs were PEGylated and passively loaded with DOX (PEG-EV-DOX). Our data suggested that the low PEG coverage of EVs might still favor EV surface protein interactions with target proteins from intratumor cells, ensuring their use as “Trojan horses” to deliver DOX to the tumor tissue. Moreover, our results showed a superior antitumor activity of PEG-EV-DOX in B16.F10 murine melanoma models in vitro and in vivo compared to that exerted by clinically applied liposomal DOX in the same tumor model. The PEG-EV-DOX administration in vivo reduced NF-κB activation and increased BAX expression, suggesting better prognosis of EV-based therapy than liposomal DOX treatment. Collectively, our results highlight the promising potential of EVs as optimal tools for systemic delivery of DOX to solid tumors.
ARTICLE | doi:10.20944/preprints202009.0510.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Hydrogel; pH-responsive; colon; targeted delivery; methotrexate
Online: 22 September 2020 (08:17:48 CEST)
The purpose of current research work was to formulate and typify gelatin and poly(vinyl) alcohol (Gel/PVA) hydrogel which would be highly pH-responsive and can able to accomplish targeted delivery of methotrexate in order to treat the colo-rectal pathologies. The primed gel/pva hydrogel discs were subjected to various physicochemical techniques i.e. swelling, diffusion co-efficient, sol-gel analysis and porosity using three altered sorts of pH (1.2, 6.8 & 7.4) phosphate buffer solutions for assessment/evaluation, and their characterization was done through Fourier transform infrared spectroscopy (FTIR) and thermal gravimetric analysis (TGA). Shape alteration and controlled methotrexate of release of Gel/PVA hydrogel have been done using three type of pH (1.2, 6.8 & 7.4) phosphate buffer mediums. Methotrexate was loaded through in-situ drug loading method due to hydrophobicity. Different kinetic models (first order & zero order kinetic), Higuchi model and Krosmere peppas model/Power law were applied to manipulate the drug release data. Physicochemical evaluation tests and drug release profile results were found insignificant (p< 0.05) in various pH mediums and dependent upon polymers concentration pH of medium and cross-linker amount. Kinetic model disclosed that release of methotrexate from Gel/PVA hydrogel follow non-Fickian diffusion method. It became concluded from this research work that release of methotrexate Gel/PVA hydrogel in targeted colon area can be achieved for treating colo-rectal disorders.
REVIEW | doi:10.20944/preprints201912.0258.v1
Subject: Biology And Life Sciences, Cell And Developmental Biology Keywords: ROS; CDDP; erythrocyte oxygen delivery capacity; AMS
Online: 19 December 2019 (11:12:08 CET)
Hypoxia is the main survival challenge that human beings encounter in high altitudes, it is also the leading cause of Acute Mountain Sickness (AMS). Studies have shown that hypoxia induces a large number of reactive oxygen species (ROS) in AMS patients, and the surge of ROS leads to the reduction of oxygen delivery capacity of erythrocyte, senescence and inflammatory impairment of erythrocyte and vascular endothelial cells to a certain extent. Through depicting a target-pathway network, our study indicates that Compound Danshen Dropping Pills (CDDP), which is one of the best-known traditional Chinese medicine used for the treatment of myocardial ischemic diseases, can improve red blood cell oxygen delivery capacity in AMS patients, alleviate tissue and organ damage, relieve a series of clinical symptoms caused by hypoxia through ROS clearance and related mechanisms. We further elucidate the active ingredients of CDDP targeting ROS related pathway by target-ingredient correspondence analysis. Tanshinone IIA, catechol and some other compounds of CDDP were identified to have certain targeting effect on ROS and ROS dependent pathways. This study provides new understandings of CDDP in clinical application on AMS.
ARTICLE | doi:10.20944/preprints201910.0027.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: PLGA; drug delivery systems; microfluidics; nanoparticles; microparticles
Online: 2 October 2019 (09:21:39 CEST)
Polymeric particles made up of biodegradable and biocompatible polymers such as poly(lactic-co-glycolic acid) (PLGA) are promising tools for several biomedical applications including drug delivery. Particular emphasis is placed on the size and surface functionality of these systems as they are regarded as the main protagonists in dictating the particle behavior in vitro and in vivo. Current methods of manufacturing polymeric drug carriers offer a wide range of achievable particle sizes, however, they are unlikely to accurately control the size while maintaining the same production method and particle uniformity, as well as final production yield. Microfluidics technology has emerged as an efficient tool to manufacture particles in a highly controllable manner. Here, we report on tuning the size of PLGA particles at diameters ranging from sub-micron to microns using a single microfluidics device, and demonstrate how particle size influences the release characteristics, cellular uptake and in vivo clearance of these particles. Highly controlled production of PLGA particles with ~100 nm, ~200 nm and >1000 nm diameter is achieved through modification of flow and formulation parameters. Efficiency of particle uptake by dendritic cells and myeloid-derived suppressor cells isolated from mice is strongly correlated with particle size and is most efficient for ~100 nm particles. Particles systemically administered to mice mainly accumulate in liver and ~100 nm particles are cleared slower. Our study shows the direct relation between the particle size varied through microfluidics and the pharmacokinetics behavior of particles, which provides a further step towards the establishment of a customizable production process to generate tailor-made nanomedicines.
ARTICLE | doi:10.20944/preprints201903.0016.v1
Subject: Medicine And Pharmacology, Obstetrics And Gynaecology Keywords: Costs, delivery, cesarean section, ethnicity, maternal morbidity
Online: 1 March 2019 (14:33:15 CET)
Recent policy and service provision recommends a woman-centered approach to maternity care and encourages the development of personalized models of clinical assistance. As ethnicity has been recognized as determinant in the risk calculation of some obstetric complication, our aim was to assess costs for birth assistance according to the maternal ethnicities. In a five-year period (2012-16) all women admitted for delivery at the Department of Obstetrics and Gynaecology, Fondazione Policlinico Universitario ‘A. Gemelli’ IRCCS, Rome, Italy were investigated. Economic evaluations were performed by using the ‘diagnosis-related group’ (DRG) approach. Cost analysis was completed by including maternal ethnicity, delivery mode and perinatal complications. A total of 18,093 patients were involved in the analysis. An overall care expense of €42.663.481 was calculated. Caucasian was the main ethnicity (90.7%), leaving the minority groups to 9.3%. Vaginal delivery (VD) was the most common mode of delivery in all ethnic clusters, with a global rate of 59.6%. Not including Asiatic women, increased CS rates were recorded in all minority ethnic groups (Maghreb (51.5%) and Afro-Caribbean (47.8%)). A double incidence of complicated VD was observed in the minority groups, primarily among Afro-Caribbean (69.9%), followed by Asiatic (64.1%), Maghreb (63.2%) and Latin-America (62.7%) patients. By logistic regression, Afro-Caribbean delivering women had a significant increased risk of complicated CS among all subgroups. Minority groups (Afro-Caribbean, in particular) increase the health care cost for birth assistance due to higher incidence of adverse perinatal outcomes.
REVIEW | doi:10.20944/preprints201810.0512.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: nanotechnology; diatom; biosilica; drug delivery; hybrid devices
Online: 22 October 2018 (16:15:47 CEST)
Diatom microalgae are the most outstanding natural source of porous silica. Diatom cell is enclosed in 3-D ordered nanopatterned silica cell wall, called frustule. The unique properties of diatoms frustule, including high specific surface area, thermal stability, biocompatibility, tailorable surface chemistry, make them really promising for biomedical applications. Moreover, diatoms are easy to cultivate in artificial environment and there is a huge availability of diatom frustules as fossil material (diatomite) in several areas of the world. For all these reasons, diatoms are an intriguing alternative to synthetic materials for the development of low-cost drug delivery systems. This review article focuses on the possible use of diatoms derived silica as drug carrier systems. The functionalization strategies of diatom micro-/nanoparticles for improving their biophysical properties, such as cellular internalization and drug loading/release kinetics, are described. In addition, the realization of hybrid diatom-based devices with advanced properties for theranostics and targeted or augmented drug delivery applications, are also discussed.
REVIEW | doi:10.20944/preprints202311.1996.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: Hydrogel Microparticles; Microgels; Bone Tissue Engineering; Bone Regeneration; Cell Delivery; Bioactive Factor Delivery; HMP-based scaffolds; HMP incorporated scaffolds
Online: 30 November 2023 (14:15:08 CET)
The loss or dysfunction of skeletal tissue often necessitates surgical intervention, particularly in cases involving trauma, tumors, or abnormal development leading to critical-sized defects. Despite autografts being considered the gold standard for bone grafts, their limitations and complications prompt the exploration of alternative approaches for bone repair and regeneration. Current advancements in bone tissue engineering have led to innovative strategies aiming to regenerate injured bone structures, providing viable alternatives to traditional autografts or allografts. Among these strategies, Hydrogel Microparticles (HMPs) have emerged as promising scaffolds due to their notable characteristics, including high porosity and mechanical tunability. HMPs play an important role in facilitating vasculature formation, mineral deposition, and overall bone tissue regeneration. HMPs, fabricated through various techniques, exhibit versatility in functions such as drug and cell delivery, structural scaffolding, and bioinks for 3D printing. In addition, these microgels can be injected for minimally invasive delivery and can display modular properties with different designs and configurations. This review exclusively focuses on the advancements in HMPs for bone regeneration, delving into synthesis and functionalization techniques while highlighting their diverse applications documented in the literature. Our aim is to shed light on the unique benefits and potential of HMPs in the intricate field of engineering bone tissue.
ARTICLE | doi:10.20944/preprints202311.1492.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Drug delivery; Hydrophobic drug; Camptothecin; Mesoporous Silica Nanoparticles
Online: 23 November 2023 (09:36:38 CET)
The practical application of a pH-responsive Nanoparticle Drug Delivery System (NDDS) in cancer treatment is often hampered by several issues such as the protection of therapeutic molecules from external stresses, inefficient targeted delivery, sustained drug release, and poor efficacy. This study presents an effective design strategy for the synthesis of a pH-sensitive controlled hydrophobic drug delivery method based on the formulation of chitosan (CS)-coated mesoporous silica nanoparticles (MSNs) through the sol-gel method, where hydrolysis takes place in the acidic medium followed by polycondensation of the hydrolyzed products. For this purpose, NH2 modified-MSNs were prepared by using tetraethyl orthosilicate (TEOS) as precursor and cetyltrimethylammonium bromide (CTAB) as a template, and 3-aminopropyltriethoxysilane (APTES) for amine modification, followed by hydrophobic drug loading and CS coating of various concentrations. Camptothecin (CPT) was used as a model drug. Fabricated monodispersed functionalized nanoparticles had sizes ranging from 200nm to 245nm with an encapsulation efficiency as high as 90%. The highest encapsulation efficiency was found for 1% CS coating, which released 50% drug in 120h at pH 6.4 and 20% at pH 7.4 respectively. These nanoformulations exhibited pH-responsive release patterns of CPT under two different pH values (pH=7.4 and pH=6.4). These results contribute to the optimization of NDDS, with potential implications for nanoformulations designed for controlled and sustained drug release particularly to tumors without affecting healthy cells owing to differences in the pH of the tumor microenvironment and the normal physiological environment of cells.
REVIEW | doi:10.20944/preprints202310.1389.v1
Subject: Medicine And Pharmacology, Otolaryngology Keywords: genetics; genomics; deafness; inner ear; cochlea; delivery; editing
Online: 23 October 2023 (10:52:29 CEST)
Hearing loss stands as the most prevalent sensory deficit among humans, posing a significant global health challenge. Projections indicate that by 2050, approximately 10% of the world's population will grapple with disabling hearing impairment. While approximately half of these cases have a genetic etiology, traditional interventions such as hearing aids and cochlear implants do not completely restore normal hearing. The absence of biological treatment has prompted significant efforts in recent years, with a strong focus on gene therapy to address hereditary hearing loss. Although several studies have exhibited promising recovery of common forms of genetic deafness in mouse models, existing challenges must be overcome to make gene therapy applicable in the near future. Herein, we summarize the primary gene therapy strategies employed over past years, provide an overview of the recent achievements in the preclinical studies for genetic hearing loss, and outline the current key obstacles to cochlear gene therapy.
ARTICLE | doi:10.20944/preprints202307.0296.v1
Subject: Public Health And Healthcare, Primary Health Care Keywords: Acceptance; antenatal care; facility-based delivery; South Africa
Online: 6 July 2023 (13:21:39 CEST)
For women giving birth, every moment of delay in receiving skilled care significantly increases the risks of stillbirth, neonatal and maternal death. More than half of all births in developing countries including South Africa, take place outside a health facility and without skilled birth attendants. This has therefore, made it difficult to achieve the Sustainable Development Goals of global reduction in maternal mortality, which is a key health challenge globally, especially in developing countries and sub-Saharan Africa in particular. The aim of this study was to explore and describe the views of pregnant women regarding facility-based delivery. Focus group discussions were used to gather information from the pregnant women. Information was collected from six groups of pregnant women who had delivered babies at the antenatal care facilities in the past years. Results showed several factors associated with the failure to use institutional delivery service, such as long distance from the health care facility, lack of transport, lack of transport fare, shortages of skilled staff, failure to disclose pregnancy, cultural and religious beliefs, and staff attitudes.
REVIEW | doi:10.20944/preprints202304.0334.v1
Subject: Chemistry And Materials Science, Nanotechnology Keywords: Cyclodextrin; , host-guest inclusion; drug delivery; interactions; application
Online: 14 April 2023 (02:52:22 CEST)
Drug delivery systems consist of cyclodextrins (CyDs) have kept constant attention for good compatibility, negligible toxicity, and improved pharmacokinetics of drugs. The unique hollow structure has endowed a lot of functions, such as inclusion of guest molecules, functional modification of active hydroxyl groups, and noncovalent interactions. Besides, the polyhydroxy structure has further extended the functions of CyDs by inter/intramolecular interactions and chemical modification. Furthermore, the versatile functions of the complex contribute to physicochemical characteristics alteration of the drugs, therapeutic talent, stimulus-responsive switch, self-assemble capability, and fiber formation. This review attempts to list the recent progress of CyDs and discuss their roles in the drug delivery system. Future perspectives of the construction of CyD-based drug delivery systems are also discussed at the end of this review, which may be the possible directions for the construction of more rational and cost-effective delivery vehicles.
REVIEW | doi:10.20944/preprints202301.0320.v1
Subject: Engineering, Electrical And Electronic Engineering Keywords: functional fluidic pumps; electrohydrodynamic pumps; flow delivery; robotics
Online: 18 January 2023 (06:45:21 CET)
In recent years, functional fluidic electrohydrodynamic (EHD) pumps have attracted considerable attention due to their remarkable features, such as simple structure, quiet operation, and energy-efficient utilization. EHD liquid pumps can be used in various industrial applications, like flow transfer, thermal management, and actuator drive. In this paper, the author reviewed EHD liquid pump research in these specific aspects: the first observation of the EHD effect, its mathematical modeling, and the choice of pump structure, electrode configuration, and working medium. Based on the review, a summary of the development and latest research on EHD pumps can be provided for the readers.
ARTICLE | doi:10.20944/preprints202209.0126.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: liposome; tumor-targeted; radiation; tumor; drug delivery; chemotherapy
Online: 8 September 2022 (14:06:26 CEST)
Targeted delivery of drugs or other therapeutic agents through internal or external triggers has been used to control and accelerate the release from liposomal carriers in a number of studies, but relatively few utilize energy of therapeutic X-rays as a trigger. We have synthesized liposomes that are triggered by ionizing radiation (RTLs) to release their therapeutic payload. These liposomes are composed of natural egg PE, DSPC, cholesterol, and DSPE-PEG-2000, and the mean size of the RTL was in the range of 114 to 133 nm, as measured by NTA. The trigger mechanism is the organic halogen, chloral hydrate, which is known to generate free protons upon exposure to ionizing radiation. Once protons are liberated, a drop in internal pH of the liposome promotes destabilization of the lipid bilayer and escape of the liposomal contents. In proof of principle studies, we assessed RTL radiation-release of fluorescent tracers upon exposure to a low pH extracellular environment or exposure to X-ray irradiation. Biodistribution imaging before and after irradiation demonstrated a preferential uptake and release of the liposomes and their cargo at the site of local tumor irradiation. Finally, a potent metabolite of the commonly used chemotherapy irinotecan, SN-38, was loaded into RTL along with near infrared (NIR) fluorescent dyes for imaging studies and measuring tumor cell cytotoxicity alone or combined with radiation exposure, in vitro and in vivo. Fully loaded RTLs were found to increase tumor cell killing with radiation in vitro and enhance tumor growth delay in vivo after three i.v. injections combined with three, 5 Gy local tumor radiation exposures compared to either treatment modality alone.
ARTICLE | doi:10.20944/preprints202112.0167.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: drug delivery; allergen; glycyrrhizic acid; allergen-specific immunotherapy
Online: 10 December 2021 (08:50:57 CET)
The most effective method of treating allergic diseases, aimed not at relieving symptoms, but at eliminating the cause of the disease, is allergen-specific immunotherapy (AIT). To reduce the risk of side effects and improve the delivery of allergens to the mucosa, various delivery systems, such as liposomes, dendrimers, nanoparticles, etc., can be used. To date, there are data on the creation of delivery systems based on glycyrrhizic acid (GA) and its derivatives, but such a delivery system has not been used for allergen-specific therapy until now. At the same time, it is known that GA has an anti-inflammatory effect, shifts the balance towards Th1, and increases the number of Treg cells, which means that in the future it can enhance the anti-allergic effect of AIT and reduce the risk of unwanted side effects. Thus, the study of the immunomodulatory effect of supramolecular complexes (micelles) of GA with extracts of allergens seems to be very promising for the development of new drugs for AIT.
REVIEW | doi:10.20944/preprints202110.0130.v1
Subject: Biology And Life Sciences, Cell And Developmental Biology Keywords: fusion protein; extracellular vesicles; target delivery; RNA sorting
Online: 8 October 2021 (09:21:36 CEST)
The advancement of precision medicine critically depends on the robustness and specificity of the carriers used for the targeted delivery of effector molecules in the human body. Numerous nanocarriers have been explored in vivo, to ensure the precise delivery of molecular cargos via tissue-specific targeting, including the endocrine part of the pancreas, thyroid, and adrenal glands. However, even after reaching the target organ, the cargo-carrying vehicle needs to enter the cell and then escape from lysosomal destruction. Most of artificial nanocarriers suffer from intrinsic limitations that either prevent them from completing the specific delivery of the cargo. In this respect, extracellular vesicles (EVs) seem to be the natural tool for payload delivery due to their versatility and low toxicity. However, EV-mediated delivery is not selective and usually short-ranged. By inserting the viral membrane fusion proteins into exosomes, it is possible to increase the efficiency of membrane recognition and also ease the process of membrane fusion. This review describes the molecular details of the viral-assisted interaction between the target cell and extracellular vesicles. We also discuss the question of the usability of viral fusion proteins in developing extracellular vesicle-based nanocarriers with higher efficacy of payload delivery. Finally, this review specifically highlights the role of Gag and RNA binding proteins in RNA sorting into extracellular vesicles.
ARTICLE | doi:10.20944/preprints202103.0779.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Adenovirus; Oncolytic; Virotherapy; Targeting; αvβ6 integrin; Systemic delivery
Online: 31 March 2021 (15:30:59 CEST)
Background: We previously developed a refined, tumor selective adenovirus, Ad5NULL-A20, har-boring tropism ablating mutations in each major capsid protein, to ablate all native means of infection. We incorporated a 20mer peptide (A20) in the fiber knob for selective infection via αvβ6 integrin, a marker of aggressive epithelial cancers. Methods: To ascertain the selectivity of Ad5NULL-A20 for αvβ6 positive tumor cell lines of pancreatic and breast cancer origin, we performed reporter gene and cell viability assays. Biodistribution of viral vectors in mice harboring xenografts with low, medium, and high αvβ6 levels was quantified by qPCR for viral genomes 48 hours post intravenous administration. Results: Ad5NULL-A20 vector transduced cells in an αvβ6 selective manner, whilst cell killing me-diated by oncolytic Ad5NULL-A20 was αvβ6 selective. Biodistribution analysis following intrave-nous administration into mice bearing breast cancer xenografts demonstrated that Ad5NULL-A20 resulted in significantly reduced liver accumulation coupled with increased tumor accumulation compared to Ad5 in all three models, with tumor: liver ratios improved as a function of αvβ6 expression. Conclusions: Ad5NULL-A20 based virotherapies efficiently target αvβ6 integrin positive tumors following intravenous administration, validating the potential of Ad5NULL-A20 for systemic ap-plications, enabling tumor selective overexpression of virally encoded therapeutic transgenes.
REVIEW | doi:10.20944/preprints202103.0771.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: cancer; gold nanoparticles; marine; drug delivery; imaging; detection
Online: 31 March 2021 (14:44:42 CEST)
Cancer is one of the health concerns in modern societies. The application of nanotechnology in medical sciences has created new possibilities for the diagnosis, imaging and the treatment of tumors in humans. The present article reviews the application of marine-based gold nanoparticles in diagnosing and treating cancer. The main data were collected from research article on the application of different marine-based gold nanoparticles in detecting and imaging cancer cells as well as in drug delivery system in treatment of cancer. Chitosan is the most used marine natural compound used to fabricate gold nanocomposites and the most reported application of this type of nano-composites is related to drug delivery system. Despite the excellent anticancer potential of different marine natural products, less studies have been conducted on the use of their compositions with gold nanoparticles in cancer therapy than other materials. Moreover, most reports available in this filed are related to their application as a drug delivery system not anticancer drug. In general, there are still challenges and limitations to the use of nanoparticles in medicine, it is hoped that in the near future nanoparticles will create a dramatic revolution not only in oncology but also in medicine.
REVIEW | doi:10.20944/preprints202012.0452.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: RNA; self-amplifying RNA; replicon; vaccine; drug delivery
Online: 18 December 2020 (11:12:44 CET)
This review will explore the four major pillars required for design and development of an saRNA vaccine: antigen design, vector design, non-viral delivery systems, and manufacturing (both saRNA and lipid nanoparticles (LNP)). In will report on the major innovations, preclinical and clinical data reported in the last five years and will discuss future prospects.
ARTICLE | doi:10.20944/preprints202012.0233.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: electronic nicotine delivery systems; nicotine addiction; vaping; cessation
Online: 9 December 2020 (15:56:46 CET)
Currently 7.6% of the U.S. young adults aged 18-24 years old currently use e-cigarettes. This study piloted three methods of ENDS cessation by measuring cessation rates, motivational techniques that contributed to cessation success, and participants’ changes after decreasing vape use. Participants were randomized into three study arms [nicotine replacement therapy (NRT) + behavioral support, vape-taper + behavioral support, self-guided] in a 1:1:1 ratio. All participants were invited to attend 9 in-person or phone appointments over the 6 month study period. At 12 weeks, 3 of 7 (42.9%) participants in the NRT + behavioral support arm, 6 of 8 (75%) vape-taper + behavioral support arm, and 7 of 9 (77.8%) self-guided arm self-reported being vape- and nicotine-free. At 6 months, 3 of 7 (42.9%) participants in the NRT + behavioral support arm, 6 of 8 (75%) vape-taper + behavioral support arm, 4 of 9 (44.4%) self-guided arm self-reported being vape- and nicotine-free. A challenge to quitting and remain quit is social pressures, but participants identified self-control and establishing new habits to be the best methods to overcome the desire to vape. Participants who received behavioral support and a vape-taper plan from pharmacists were more likely to be vape- and nicotine-free at 6 months.
ARTICLE | doi:10.20944/preprints202011.0410.v1
Subject: Computer Science And Mathematics, Software Keywords: Agile software development; DevOps; Cloud Computing; Continuous Delivery
Online: 16 November 2020 (10:39:44 CET)
DevOps is an emerging practice to be followed in the Software Development life cycle. The name DevOps indicates that it’s an integration of the Development and Operation team. It is followed to integrate the various stages of the development cycle. DevOps is an extended version of the existing Agile method. DevOps aims at continuous integration, Continuous Delivery, Continuous Improvement, faster feedback and security. This paper reviews the building blocks of DevOps, challenges in adopting DevOps, Models to improve DevOps practices and Future works on DevOps
ARTICLE | doi:10.20944/preprints202010.0573.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: implant; bacterial cellulose; patch; myocardial infarction; cell; delivery
Online: 28 October 2020 (08:59:09 CET)
Biologic scaffolds have become an attractive approach for repairing the infarcted myocardium and have been shown to facilitate constructive remodeling in injured tissues. This study aimed to investigate the possible utilization of bacterial cellulose membrane patch containing cocultured cells to limit the myocardium's post-infarction pathology. Myocardial infarction was induced by ligating the left anterior descending coronary artery in 45 Wistar rats, and patches with or without cells were attached to the hearts. After one week, the animals underwent echocardiography for assessing ejection fraction and left ventricular end-diastolic and end-systolic volumes. Following the patch formation, cocultured cells retained viability of >90% over 14 days in culture. The patch was applied to the myocardial surface of the infarcted area after staying 14 days in culture. Interestingly, the bacterial cellulose membrane without cellular treatment showed higher preservation of cardiac dimensions; however, we did not observe improvement in the left ventricular ejection fraction of this group compared to coculture treated membranes. Our results demonstrated an important role for bacterial cellulose in supporting cells known to produce cardioprotective soluble factors and may thus provide effective future therapeutic outcomes for patients suffering from ischemic heart disease.
ARTICLE | doi:10.20944/preprints201901.0215.v1
Subject: Biology And Life Sciences, Food Science And Technology Keywords: Maternal nutrition; Breast milk; Premature delivery; Milk composition
Online: 22 January 2019 (11:27:30 CET)
(1) Background: Premature infants require mothers’ milk fortification to meet nutrition needs, but breast milk composition may be variable leading to a risk of inadequate nutrition. We aimed at determining factors influencing mothers’ milk macronutrients. (2) Methods: Milk samples were analyzed for the first 5 weeks after premature delivery, by infrared spectroscopy. Mothers’ nutritional intake data were obtained during standardized interviews with dieticians then analyzed with reference software. (3) Results: Composition of 367 milk samples from 81 mothers was (Median [range]g/100mL): Carbohydrates 6.8[4.4-7.3], lipids 3.4[1.3-6.4], proteins 1.3[0.1-3.1]. There was a relationship of milk composition with mothers’ carbohydrates intake only (r=0.164; p<.01). Postnatal age was correlated with milk proteins (r=-0.505 p<.001) & carbohydrates (r=+0.202, p<.001). Multiple linear regression analyses showed (coefficient) a relationship between milk proteins r=0.547 and postnatal age (-0.028), carbohydrates intake (+0.449) and the absence of maturation (-0.066); and between milk lipids r=0.295 and carbohydrates intake (+1.279) and smoking (-0.557). Finally, between milk carbohydrates concentration r=0.266 and postnatal age (+0.012) and smoking (-0.167). (4) Conclusions: Variability of mothers’ milk composition is differentially associated for each macronutrient with maternal carbohydrates intake, antenatal steroids, smoking, and postnatal age. Improvement in milk composition could be achieved by modification of these related factors.
REVIEW | doi:10.20944/preprints201810.0027.v1
Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: Infants, Newborn, Neonatal Resuscitation, Chest compressions, Delivery room
Online: 2 October 2018 (14:58:58 CEST)
Annually, an estimated 13-26 million newborns need respiratory support and 2-3 million newborns need extensive resuscitation, defined as chest compression and 100% oxygen with or without epinephrine in the delivery room. Despite such care, there is a high incidence of mortality and short-term neurologic morbidity. The poor prognosis associated with receiving chest compression alone or with medications in the delivery room raises questions as to whether improved cardiopulmonary resuscitation methods specifically tailored to the newborn could improve outcomes. This review discusses the current recommendations, mode of action, different compression to ventilation ratio, continuous chest compression with asynchronous ventilations, chest compression and sustained inflation optimal depth, and oxygen concentration during cardiopulmonary resuscitation.
ARTICLE | doi:10.20944/preprints201807.0365.v1
Subject: Social Sciences, Library And Information Sciences Keywords: Traditional; Communication; Media; Rural; Information Service Delivery; Adolescent
Online: 19 July 2018 (15:25:56 CEST)
This research work examined the various communication media used in the rural areas for the purpose of conveying messages to Adolescents in the selected communities in Obio/Akpor Local Government Area of Rivers State, Nigeria - Woji, Rumuigbo, Rumuola, Rumuokwuta and Elelenwo communities. The Taro Yammane Statistical formula for determination of sample size was used in drawing a sample of 363 respondents from a population of 3,630 Adolescents. The simple random sampling method was used in the distribution of the questionnaire to target respondents in the selected communities. Two hundred and eighty two (282) copies of the questionnaire were returned valid, and data from them was analysed and interpreted with the use of frequency tables and percentages. The result shows that traditional communication media is still relevant in the dissemination of information to rural dwellers in general and to Adolescents in particular. The agencies that make use of these media are; village authority, age groups, etc. The research work recommend among others that the government and rural dwellers should hold our traditional and cultural values in high esteem through the use of these media, harmonizing the use of traditional communication media and modern media for effective rural information service delivery.
ARTICLE | doi:10.20944/preprints201802.0012.v3
Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: chitosan; self-assembled; polyelectrolyte complex; nanoparticle; drug delivery
Online: 21 February 2018 (16:00:38 CET)
Chitosan is a cationic polysaccharide usually obtained by alkaline deacetylation of chitin poly(N-acetylglucosamine). It is biocompatible, biodegradable, mucoadhesive and non-toxic. These excellent biological properties make chitosan a good candidate for a platform in developing drug delivery systems having improved biodistribution, increased specificity and sensitivity, and reduced pharmacological toxicity. In particular, chitosan nanoparticles are found to be appropriate for non-invasive routes of drug administration: oral, nasal, pulmonary and ocular routes. These applications are facilitated by the absorption-enhancing effect of chitosan. Many procedures for obtaining chitosan nanoparticles have been proposed. Particularly, the introduction of hydrophobic moieties into chitosan molecules by grafting to generate a hydrophobic-hydrophilic balance promoting self-assembly is a current and appealing approach. The grafting agent can be a hydrophobic moiety forming micelles that can entrap lipophilic drugs or it can be the drug itself. Another suitable way to generate self-assembled chitosan nanoparticles is through the formation of polyelectrolyte complexes with polyanions. This paper reviews the main approaches for preparing chitosan nanoparticles by self-assembly through both procedures and illustrates the state of the art of their application in drug delivery.
REVIEW | doi:10.20944/preprints201702.0036.v1
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: pulmonary arterial hypertension; prostacyclin; nanoparticle; drug delivery system
Online: 13 February 2017 (09:27:09 CET)
Nanoparticles have been used as a novel drug delivery system. Drug-incorporated nanoparticles for local delivery might optimize the efficacy and minimize the side effects of drugs. The efficacy and safety of intratracheal administration of prostacyclin analog (beraprost)-incorporated nanoparticles and imatinib, a PDGF-receptor tyrosine kinase inhibitor, -incorporated nanoparticles in Sugen-hypoxia-normoxia or monocrotaline rat models of PAH and in human PAH-pulmonary arterial smooth muscle cells have been reported. The use of inhaled drug-incorporated nanoparticles might be a novel approach for treatment of PAH.
REVIEW | doi:10.20944/preprints201812.0170.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: bacterial nanocellulose; nanofibrillated nanocellulose; animal nanocellulose; algal nanocellulose; tissue engineering; tissue repair; wound dressing; cell delivery; drug delivery; antimicrobial properties
Online: 14 December 2018 (06:44:53 CET)
Nanocellulose is cellulose in the form of nanostructures, i.e. features not exceeding 100 nm at least in one dimension. These nanostructures include nanofibrils, e.g. in bacterial cellulose; nanofibers, e.g. in electrospun matrices; nanowhiskers and nanocrystals. These structures can be further assembled into bigger 2D and 3D nano-, micro- and macro-structures, such as nanoplatelets, membranes, films, microparticles and porous macroscopic matrices. There are four main sources of nanocellulose: bacteria (Gluonacetobacter), plants (trees, shrubs, herbs), algae (Cladophora) and animals (Tunicata). Nanocellulose has emerged for a wide range of industrial, technology and biomedical applications, e.g. for adsorption, ultrafiltration, packaging, conservation of historical artifacts, thermal insulation and fire retardation, energy extraction and storage, acoustics, sensorics, controlled drug delivery, and particularly for tissue engineering. Nanocellulose is promising for use in scaffolds for engineering of blood vessels, neural tissue, bone, cartilage, liver, adipose tissue, urethra and dura mater, for repairing connective tissue and congenital heart defects, and for constructing contact lenses and protective barriers. This review is focused on applications of nanocellulose in skin tissue engineering and wound healing as a scaffold for cell growth, for delivering cells into wounds, and as a material for advanced wound dressings coupled with drug delivery, transparency and sensorics. Potential cytotoxicity and immunogenicity of nanocellulose are also discussed.
REVIEW | doi:10.20944/preprints202311.1984.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: nanoquercetin; extracellular vesicles; hepatocellular carcinoma; therapeutics; anticancer; drug delivery
Online: 1 December 2023 (03:08:11 CET)
Over the few decades, cancer-associated mortalities and morbidities were continuously increased worldwide despite sophisticated technological advancements. Pharmaceutical interventions associated with drugs exhibit a high degree of side effects and toxicities in addition to very high costs. Subsequently, to reduce or to vanish the side effects and high costs, researchers are now exploring natural bioactive compounds such as quercetin in its nanoformulations along with biologics as cargo delivery vehicles. Quercetin along with mesenchymal stromal lineage-derived extracellular vesicles (EVs) possesses an anti-cancer potential that can be explored to treat hepatocellular carcinoma (HCC). Exerting enhanced effect, nano quercetin synergistically with EVs triggers the anti-cancer mechanisms by regulating and dysregulating several signalling mechanisms including NF-κB, p53, JAK/STAT, MAPK, Wnt/β-catenin and PI3K/AKT, in addition to PBX3/ERK1/2/CDK2, and miRNAs modulation. In addition, findings regarding the potential checkpoints of anti-cancer signalling pathways were investigated that offer opportunities to develop engineered EVs incorporated with nano quercetin for the development of novel therapeutics to treat HCC in future. In this present mechanistic review, we abridged the regulation of such signalling mechanisms synergetic approach of nano quercetin and EVs. The regulatory role of EVs in the manifestation of innumerable miRNAs has also been tailed with special context to HCC.
ARTICLE | doi:10.20944/preprints202310.2099.v1
Subject: Medicine And Pharmacology, Veterinary Medicine Keywords: Oral vaccine; Salmonella delivery; porcine circovirus type 2; PCV2d
Online: 31 October 2023 (14:35:37 CET)
Oral vaccines are highly envisaged for veterinary applications due to their convenience and ability to induce protective mucosal immunity as the first line of defense. The present investigation harnessed live-attenuated Salmonella Typhimurium to orally deliver novel expression vector systems containing the Cap and Rep genes from porcine circovirus type 2 (PCV2), a significant swine pathogen. The antigen expression by the vaccine candidates JOL2885 and JOL2886, comprising eukaryotic pJHL204 and pro-eukaryotic expression pJHL270 plasmids respectively, was confirmed by western blot and IFA. We evaluated their immunogenicity and protective efficacy through oral vaccination in a mouse model. This approach elicited both mucosal and systemic immunity against PCV2d. Oral administration of the candidates induced PCV2-specific sIgA, serum IgG antibodies, and neutralizing antibodies, resulting in reduced viral loads in the livers and lungs of PCV2d-challenged mice. T-lymphocyte proliferation and flow-cytometry assays confirmed enhanced cellular immune responses after oral inoculation. The synchronized elicitation of both Th1 and Th2 responses was also confirmed by enhanced expression of TNF-α, IFN-γ, IL-4, MHC-I, and MHC-II. Our findings highlight the effectiveness and safety of the constructs with an engineered-attenuated S. Typhimurium, suggesting its potential application as an oral PCV2 vaccine candidate.
ARTICLE | doi:10.20944/preprints202310.1478.v1
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: Public health; health service delivery; human resources; vulnerability; sustainability
Online: 24 October 2023 (08:11:28 CEST)
The COVID-19 pandemic, which has affected the entire world, has not only created a number of emerging issues for each country, especially in the field of public health, but has also provided a number of opportunities for risk management, alternative strategies and completely new ways of looking at challenges. This paper examines the COVID-19 pandemic response in Türkiye and the possible implications of the experience for future responses to other health emergencies and disaster risk management, based on the lessons learned. This study uses publicly available literature from government, private sector, and academic sources to analyse the conflicts, changes and lessons learned during the COVID-19 pandemic, which are components of the World Health Organization (WHO) Health Emergency and Disaster Risk Management (Health EDRM) framework. The COVID-19 experience in Türkiye has several aspects, including the significant role of healthcare workers, the existence of an effective health system accustomed to emergencies, applications based on information technologies, partial transparency of public authorities in providing information, and socio-cultural environment related to cooperation on prevention strategies, including wearing masks and vaccination. Challenges in Türkiye include distance learning in schools, lockdowns that particularly affect the elderly, ensuring environmental sustainability, hesitation about the effectiveness of social/financial support programmes, socio-cultural trivialisation of pandemics after a while, and relaxation of prevention strategies. Lessons learned from the COVID-19 pandemic include the value of transparency in public health/healthcare information, the strengthening of all aspects of the health system in terms of health workers, and the importance of a balanced economy prepared for foreseeable risks.
ARTICLE | doi:10.20944/preprints202310.0299.v1
Subject: Medicine And Pharmacology, Pharmacy Keywords: API; PLGA nanoparticles; HA; CD44; colon cancer; targeted delivery
Online: 5 October 2023 (14:22:23 CEST)
Apigenin (API) possesses excellent antitumor properties, but its limited water solubility and low bioavailability restrict its therapeutic impact. Thus, a suitable delivery systems is needed to overcome these limitations and improve the therapeutic efficiency. Poly (lactic-co-glycolic acid) (PLGA) is a copolymer extensively utilized in drug delivery. Hyaluronic acid (HA) is a major extracellular matrix and can specifically bind with CD44 on colon cancer cells. Chitosan (CS) can serve as an intermediate binding with HA and PLGA. Herein, we aimed to perpare receptor-selective HA-coated PLGA nanoparticles (NPs) for colon cancer with high expression of CD44. Firstly, API was encapsulated in PLGA to obtain PLGA-API-NPs, which were then sequentially combined with CS and HA to form HA-coated PLGA NPs. HA coated PLGA NPs had a stronger sustained-release capability. Cellular uptake of HA coated PLGA NPs was enhanced in HT-29 cells with high expression of CD44. HA-PLGA-DiR-NPs can target specificity towards the HT-29 ectopic tumor model. Overall, HA coated PLGA NPs was an effectively drug deliver platform for API in treatment of colon cancer with high expression of CD44.
REVIEW | doi:10.20944/preprints202310.0024.v1
Subject: Engineering, Bioengineering Keywords: contact lens; drug delivery; bioavailability; composite; gas-permeable; hydrogel
Online: 1 October 2023 (11:18:39 CEST)
The number of people affected by eye conditions is growing every year, due to the popularity of electronic devices and an aging population. In the world of medicine, accomplishing eye medication administration has always been a difficult task. Despite the fact that there are many eye drops on the market, most of them have important limitations due to quick clearance mechanisms and ocular barriers. One solution with tremendous potential is the contact lens used as medication delivery vehicle to bypass this constraint. Therapeutic contact lenses for ocular medication delivery have attracted a lot of attention because they have the potential to improve ocular bioavailability, patient compliance, and reduce side effects. However, it is essential not to compromise essential features such as water content, optical transparency, and modulus in order to target successful in vitro and in vivo sustained drug delivery profile from impregnated contact lenses. Aside from difficulties like drug stability and burst release, the changing of lens physical and chemical properties caused by therapeutic or non-therapeutic components can limit the commercialization potential of pharmaceutical-loaded lenses. Research has progressed towards bioinspired techniques and smart materials to improve the efficacy of drug-eluting contact lenses. The bioinspired method uses bioinspired polymeric materials to improve biocompatibility, a specialized molecule recognition technique called molecular imprinting, or a stimuli-responsive system to improve biocompatibility and support drug delivery efficacy of drug-eluting contact lenses. This review encompasses strategies of material design, lens manufacturing and drug impregnation under the current auspices in ophthalmic therapies and projects an outlook onto future opportunities in the field of eye conditions management by means of active principles-eluting contact lens.
REVIEW | doi:10.20944/preprints202309.0901.v1
Subject: Chemistry And Materials Science, Materials Science And Technology Keywords: hydrogel; natural polymer; drug delivery; tissue engineering; wound healing
Online: 14 September 2023 (04:39:02 CEST)
Hydrogels prepared from natural polymer have attracted extensive attentions in biomedical fields such as drug delivery, wound healing, and regenerative medicine due to their good biocompatibility, degradability and flexibility. This review outlines the commonly used natural polymer in hydrogel preparation, including cellulose, chitosan, collagen/gelatin, alginate, hyaluronic acid and starch. The polymeric structure and process/synthesis of natural polymers are illustrated, and natural polymer-based hydrogels including the hydrogel formation and properties are elaborated. Subsequently, the biomedical application of hydrogels based on natural polymer in drug delivery, tissue regeneration, wound healing and other biomedical field is summarized. Finally, the future perspectives of natural polymers and hydrogels based on them are discussed. For natural polymer, novel technologies such as enzymatic and biological methods are developed to improve the structural properties and the development of new natural based polymers or natural polymer derivatives with high performance is still very important and challenging. For natural polymer-based hydrogels, novel hydrogel materials, like double-network hydrogel, multifunctional composite hydrogels and hydrogel microrobots are designed to meet the advanced requirements in biomedical application, and new strategies such as dual-crosslinking, microfluidic chip, micropatterning and 3D/4D bioprinting, have been explored to fabricate advanced hydrogel materials with designed properties for biomedical application. Overall, natural polymeric hydrogels have attracted increasing interests in biomedical application, and the development of novel natural polymer-based materials and new strategies/methods for hydrogel fabrication is badly desirable and still challenging.
ARTICLE | doi:10.20944/preprints202308.1656.v1
Subject: Chemistry And Materials Science, Materials Science And Technology Keywords: Hollow mesoporous silica; Alkylammonium; Fludarabine; Drug delivery; Cancer therapy
Online: 24 August 2023 (02:20:25 CEST)
In this work, alkylammonium-functionalized hollow mesoporous silica as nonocarrier of drugs was synthesized to realize enhanced cancer therapy by pH stimuli for sustained drug release. First, functionalized hollow mesoporous silica nanoparticles (Hollow MSNs) were synthesized using dodecyl dimethyl(3-sulfopropyl)ammonium hydroxide (DDAPS), sodium dodecyl sulfate (SDS), and triethanolamine as structure-directing agents, and tetraethyl orthosilicate (TEOS) and N-trimethoxysilypropyl-N,N,N-trimethylammonium chloride (TMAPS) as silica sources under basic condition via the sol-gel process. The structure and morphology of the alkylammonium-functionalized hollow mesoporous silica nanoparticles (Hollow MSN-N+CH3) were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), N2 adsorption-desorption analysis, and Fourier-transform infrared (FT-IR) spectroscopy. The functionalized hollow MSNs had a particle size of about 450 nm and a shell thickness of about 60 nm with uniform size. The nanoparticle had a surface area of 408 m2g-1, pore volume of 0.8 cm3g-1 and a uniform pore diameter of 45.9 Å. In the cancer cell viability test with MCF-7 cell, fludarabine-incorporated and alkylammonium-functionalized hollow mesoporous silica nanoparticles (Flu/Hollow MSN-N+CH3) showed excellent cancer cell death comparable with pure fludarabine drug with the controlled drug release by pH stimuli. It is considered that our current materials have the potential applicability as pH-responsive nanocarriers in the field of cancer therapy.
REVIEW | doi:10.20944/preprints202308.1487.v1
Subject: Engineering, Chemical Engineering Keywords: microchannels; droplet; hydrophilic compound; hydrophobic compound; drug delivery; emulsion
Online: 22 August 2023 (03:38:29 CEST)
Microfluidic technology has become a powerful tool for several applications in chemistry, physics, biology, and engineering. Benefiting from the advantages of flowing fluids in the laminar regime, droplet-based microfluidics enable the development of various delivery systems based on food-grade emulsions, such as multiple emulsions, microgels, microcapsules, solid lipid micro-particles, and giant liposomes. Besides, by manipulating fluids on a micrometer scale with low-energy demand, it is possible to control the size, shape, and dispersity of droplets generated, which makes microfluidic emulsification an excellent strategy to modulate delivery system properties depending on the entrapped compound type. Thus, this review points out the most current advances in droplet-based microfluidic processes, in which food-grade materials were successfully utilized to develop simple and complex delivery systems. In that context, we sum-marized the principles of droplet-based microfluidics, introducing the most common microde-vices geometries, manufacturing materials, and forces involved in the different droplet generation processes within the microchannels. Subsequently, the encapsulated compound type, classified as lipophilic or hydrophilic functional compounds, was used as a starting point to present current advances in delivery systems based on food-grade emulsions and assembly using microfluidic technologies. Finally, we discuss the limitations and perspectives of scale-up in droplet-based microfluidic approaches, including the challenges that have limited the transition of microfluidic processes from lab-scale to industrial-scale.
ARTICLE | doi:10.20944/preprints202307.1878.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: Microparticles; PEG; PLGA; coaxial flow; phase separation; drug delivery
Online: 27 July 2023 (09:38:27 CEST)
Polymeric microparticles of polyethyleneglycol-polylactic acid-co-glycolic acid (PEG-PLGA) are widely used as drug carriers for a variety of applications due to their unique characteristics. Herein, we developed a novel method for the synthesis of uniformly sized microparticles via coaxial flow-phase separation. The study evaluated the effect of various process parameters on microparticle size and polydispersity including polymer concentration, stirring rate, surfactant concentration, and the organic/aqueous phase flow rate and volume ratio. The results demonstrated that stirring rate and polymer concentration had the most significant impact on the mean particle size and distribution whereas surfactant concentration had the most substantial impact on the morphology of particles. Several microparticle formulations yielding particle sizes in the range of (5-50 µm), morphology, and concentration were synthesized as a demonstration of the tunability and scalability of this method. Notably, by controlling the process parameters microparticles of less than ~ 7 μm could be made using polymer concentrations varying by an order of magnitude. Finally, we demonstrated the tunability and scalability of this method by showing a 10-fold increase in encapsulation efficiency, a 3-fold increase in drug loading of a model hydrophilic drug, and modified release kinetics in microparticle formulations of comparable sizes but different polymer concentrations.
ARTICLE | doi:10.20944/preprints202306.2020.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: Bioresponsive; gelatin; hyaluronic acid; bioprinting; cell-delivery; tissue engineering
Online: 29 June 2023 (02:20:28 CEST)
Development of bioresponsive extrudable hydrogels for 3D bioprinting is imperative to address the growing demand for scaffold design and efficient and reliable methods of tissue engineering and regenerative medicine. This study proposed genipin-crosslinked gelatin-hyaluronic acid hydrogel bioink with different amounts of gelatin tailored for 3D bioprinting, focusing on high cell density loading and less artificial extra-cellular matrix (ECM) effect, as well as exploring their potential applications in tissue engineering. The bioresponsiveness of these hydrogel scaffolds was successfully evaluated in different physiological conditions. 3D and four-axis printing of complex structures such as shapes of hollow tube, star, pyramid, and four-axis tubular scaffolds prove the hydrogel’s high extrusion ability and post-printing shape fidelity. Cytocompatibility and high cell density 3D bioprinting using this moderately stable hydrogel exhibit high potential for precise cell-delivery modes in tissue engineering as well as regenerative medicine.
REVIEW | doi:10.20944/preprints202306.1118.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: Cancer; Drug delivery systems; Polymeric hydrogels; Stimuli-responsive materials
Online: 15 June 2023 (09:49:21 CEST)
Polymeric hydrogels are promising polymeric functional materials that have been widely used in the biomedical field as an emerging carrier of various therapeutic agents. Polymeric hydrogels as a carrier of therapeutics can leverage therapeutically beneficial outcomes of drug delivery than systemic chemotherapy and can provide spatial and temporal control over the release of various therapeutic agents. Polymeric hydrogels are cross-linked three-dimensional networks constructed by hydrophilic polymers and they are capable of absorbing and re-taining a large amount of water. Polymeric hydrogels share many physiochemical features with natural tissues due to their water abundance, biomimetic microstructure, and intrinsic flexibility. Polymeric hydrogels have excellent biocompatibility, biodegradability, and lower toxicity. Polymeric hydrogels enhance the convenience and efficiency of drug delivery by assisting in situ gelation and controlling drug release by changing their volume and other properties when it encounters some stimuli (e.g., heat, pH, light, and ultrasound). This review aims to outline the overview of polymeric hydrogels, properties, types, advantage, disadvantages, characteri-zation, and their application with present status and future perspective used for the delivery of therapeutics in pharmaceutical and biomedical sciences.
ARTICLE | doi:10.20944/preprints202306.0451.v1
Subject: Chemistry And Materials Science, Organic Chemistry Keywords: Synthesis; Amphiphilic Macrocycle; Biocompatibility; Amphotericin-B; drug delivery; pharmacokinetics
Online: 6 June 2023 (11:46:01 CEST)
The supramolecular based macrocyclic amphiphiles have attracted great attention in the field of drug delivery due to their unique self-assembling nature. Therefore, these macrocycles are used as nanocarriers for the delivery of poor water soluble drugs, and also for those which have lower permeability, and cannot cross the barrier to reach the desired site. Herein, we design and synthesized a new supramolecular amphiphilic macrocycle to overcome these problems. The macrocycle was synthesized in two steps. In first step 4-hydroxybenzaldehyde was treated with 1-bromotetradecane to obtain a derivatized product which was then treated with resorcinol to cyclize and get calix(4)resorcinarene based supramolecular amphiphilic macrocycle. The synthesized macrocycle and intermediate products were characterized by Mass spectrometry, IR and 1H-NMR spectroscopic techniques. The amphiphile was screened for biocompatibility studies, vesicles formation, and then Amphotericin-B was loaded in the supramolecular amphiphile based vesicles and was characterized for shape, size, homogeneity, surface charge, drug entrapment, in-vitro release profile and stability through atomic force microscopy (AFM), Zetasizer, HPLC and FT-IR. Amp-B loaded macrocycle based vesicles were investigated for in-vivo bioavailability in rabbits. The synthesized macrocycle was nontoxic in cancer cells, hemo-compatible and safe in mice. The drug-loaded macrocycle based vesicles appeared spherical, nano-ranged, and homogeneous in size with negative surface charge and were able to load an increased amount of drug. The vesicles are stable upon storage and when incubated with gastric simulated fluid. Amp-B increased oral bioavailability was achieved when delivered in synthesized macrocycle based vesicles. These results point out that the synthesized supramolecular amphiphile is an efficient nanocarrier to enhance the oral bioavailability of lipophilic drugs
ARTICLE | doi:10.20944/preprints202305.1385.v1
Subject: Chemistry And Materials Science, Nanotechnology Keywords: smart drug delivery system; nanomaterials; poly(methacrylic acid); photoluminescence
Online: 19 May 2023 (05:39:42 CEST)
Nanomaterials such as pH-responsive polymers are promising for targeted drug delivery systems, due to the difference in pH between tumor and healthy regions. However, there is a significant concern about the application of these materials in this field due to their low mechanical resistance, which can be mitigated by combining these polymers with mechanically resistant inorganic materials such as mesoporous silica nanoparticles (MSN) and hydroxyapatite (HA). Mesoporous silica has interesting properties such as high surface area and hydroxyapatite has been widely studied to aid in bone regeneration, providing special properties adding multifunctionality to the system. Furthermore, fields of medicine involving luminescent elements such as rare earth are an interesting option in cancer treatment. The present work aims to obtain a pH-sensitive hybrid system based on silica and hydroxyapatite with photoluminescent and magnetic properties. The nanocomposites were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), nitrogen adsorption methods, CHN elemental analysis, Zeta Potential, scanning electron microscopy (SEM), and transmission electron microscopy (TEM), vibrational sample magnetometry (VSM), and photoluminescence analysis. Incorporation and release studies of the antitumor drug doxorubicin were performed to evaluate the potential use of these systems in targeted drug delivery. The results showed the luminescent and magnetic properties of the materials and showed suitable characteristics for application in the release of pH-sensitive drugs.
REVIEW | doi:10.20944/preprints202305.0628.v1
Subject: Medicine And Pharmacology, Dermatology Keywords: atopic dermatitis; skin inflammation; natural products; nanotechnology; topical delivery
Online: 9 May 2023 (09:45:26 CEST)
Atopic dermatitis (AD) is a chronic eczematous inflammatory disease that may arise from environmental, genetic and immunological factors. Despite the efficacy of current treatment options like corticosteroids, such approaches are mainly focused on symptoms relief, and may present certain undesirable side effects. In recent years, investigation regarding isolated natural compounds, oils, mixtures and/or extracts, have gained scientific attention because of their high efficiency and moderate to low toxicity. Despite their promising therapeutic effects, the applicability of such natural health care solutions is somehow limited by their instability, poor solubility, and low bioavailability. Therefore, novel nanoformulation-based systems have been designed to overpass these limitations, thus enhancing the therapeutic potential, by promoting the capacity of these natural drugs to properly exert their action in AD-like skin lesions. For the best of our knowledge, this is the first literature review that focused on summarizing the last nanoformulation-based solutions loaded with natural ingredients, and specifically for the management of AD. We suggest that future studies should focus on robust clinical trials that may confirm the security and effectiveness of such natural-based nanosystems, thus paving the way for more reliable AD treatments.
ARTICLE | doi:10.20944/preprints202304.0106.v1
Subject: Biology And Life Sciences, Virology Keywords: Feline Infectious Peritonitis; Rottlerin; Drug Delivery System; Liposome; Antivirals
Online: 7 April 2023 (03:40:34 CEST)
Rottlerin(R) is a natural extract from Mallotus philippensis with antiviral properties. Feline Infectious Peritonitis (FIP) is a fatal disease characterized by systemic granulomatous inflammation and high mortality, with no established prevention or cure. We investigated antiviral effect of liposome loaded R, Rottlerin-liposome(RL) against Feline infectious peritonitis virus (FIPV), the causative agent. We demonstrated that R and RL inhibited FIPV replication in dose dependently with a PKCδ related manner, not only in the early endocytosis step but also in the late step of replication. RL resolved the low solubility issue of rottlerin and improved its inhibition efficacy at the cellular level. Based on these findings, we suggest that RL has a value for further research as a potential antiviral agent against FIPV.
ARTICLE | doi:10.20944/preprints202303.0546.v1
Subject: Engineering, Bioengineering Keywords: Hydrogel Microneedle; Transdermal; Drug Delivery; Diffusion time; Numerical Simulation
Online: 31 March 2023 (09:31:25 CEST)
Hydrogel microneedles are a promising technology for the delivery of different types of medicines locally and painlessly, as well as ISF extraction. As the hydrogel microneedles are inserted into the tissue, they swell and release drugs. To improve the effectiveness of this technology in delivering medicine at controlled and desirable doses and intervals, a deep understanding of the mechanism of drug delivery inside the microneedles is required. In this work, drug diffusion inside a tapered microneedle is investigated using numerical simulation. The microneedle is divided into many small elements, and the mass transfer equation of meloxicam is solved in each element over time. The skin is simulated as the sink in the microneedle surface for drug absorption. Simulations are performed for different sizes of microneedles. For a microneedle with a height of 500 µm and a base diameter of 250 µm, the drug completely penetrates the skin within 3.2 seconds. The rate of drug diffusion from the tip of the microneedle is higher than diffusion from the side area near the microneedle base. The obtained data demonstrate that in addition to the height and the base diameter, the microneedle’s aspect ratio, h/d, also affects the time of drug diffusion. We present a nonlinear equation to predict the time of complete drug diffusion as a function of the microneedle geometrical parameter, including the height and base diameter. The proposed equation calculates the total drug diffusion time with an error of less than 7% for all studied cases. Predicting drug diffusion patterns inside microneedles can be helpful in the biomedical field, especially in the drug-controlled release system for the optimization of drug delivery.
ARTICLE | doi:10.20944/preprints202211.0069.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: reconstituted lipid nanoparticles; drug delivery systems; solvent diffusion method
Online: 3 November 2022 (03:57:32 CET)
Nanomedicine holds great potential to devise better drug delivery systems (DDSs). However, many reported nanomedicines still fall short of commercial requirements including specific targetability, scale-up manufacturing and safety. Cell/tissue based carriers, including cell membrane vehicle and exosome, are biocompatible and targeting platforms but usually suffered from low yields and unstable reproducibility. Here in this study, we proposed the concept and preparation of reconstituted lipid nanoparticles (rLNPs) to develop highly reproducible cell/tissue based lipid nanoparticles (LNPs) for drug delivery, which holds the potential as a versatile drug delivery platform. The whole lipids of cell or tissue were firstly extracted and then prepared into rLNPs using solvent diffusion method. In this way, the preparation of ultra-small (~20 nm) rLNPs can be easily applied to both cell (mouse breast cancer cell line, 4T1) and tissue (mouse liver tissue). Our results demonstrated that mouse liver tissue derived rLNPs can be further labeled/modified with imaging, targeting or other functional moieties. Furthermore, rLNPs were highly biocompatible and capable of loading different drugs including doxorubicin hydrochloride (Dox) and curcumin (Cur). Most importantly, Dox loaded rLNPs (rLNPs/Dox) showed preferable in vitro and in vivo anticancer performance. Therefore, rLNPs might be a versatile drug delivery platform for future application in the treatment of a variety of diseases.
REVIEW | doi:10.20944/preprints202201.0146.v1
Subject: Chemistry And Materials Science, Nanotechnology Keywords: Nanomedicine; drug resistance; lung cancer; chemotherapeutic agents; drug delivery
Online: 11 January 2022 (13:48:22 CET)
Lung cancer (LC) is one of the leading causes of cancer occurrence and mortality worldwide. Treatment of patients with advanced and metastatic LC presents a significant challenge as malignant cells use different mechanisms to resist chemotherapy. Drug resistance (DR) is a complex process that occurs due to a variety of genetic and acquired factors. Identifying the mechanisms underlying DR in LC patients and possible therapeutic alternatives for more efficient therapy is a central goal of LC research. Advances in nanotechnology resulted in the development of targeted and multifunctional nanoscale drug constructs. The possible modulation of the components of nanomedicine, their surface functionalization, and encapsulation of various active therapeutics provide promising tools to bypass crucial biological barriers. These attributes enhance the delivery of multiple therapeutic agents directly to the tumor microenvironment (TME), resulting in reversal of LC resistance to anticancer treatment. This review provides a broad framework for understanding the different molecular mechanisms of DR in lung cancer; presents novel nanomedicine therapeutics aimed to improve the efficacy of treatment of various forms of resistant LC; outlines current challenges in using nanotechnology for reversing DR; and discusses the future directions for clinical application of nanomedicine in management of LC resistance.
REVIEW | doi:10.20944/preprints202201.0035.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: Cellulose; Biomedical; Wound healing; Drug delivery; Antibacterials; Tissue engineering
Online: 5 January 2022 (11:00:57 CET)
There are various biomaterials in nature, but none fulfills all the requirements. Cellulose, eco-friendly material-based biopolymers, have been advanced biomedicine to satisfy most market demand and circumvent many ecological concerns. This review aims to present an overview of the state of the art in cellulose's knowledge and technical biomedical applications. It included an extensive bibliography of recent research findings for fundamental and applied investigations. The chemical structure of cellulose allows modifications and simple conjugation with several materials, including nanoparticles, without tedious efforts. Cellulose-based materials were used for biomedicine applications such as antibacterial agents, antifouling, wound healing, drug delivery, tissue engineering, and bone regeneration. They advanced the applications to be cheap, biocompatible, biodegradable, easy for shaping and processing into different forms, with suitable chemical, mechanical and physical properties.
REVIEW | doi:10.20944/preprints202109.0496.v1
Subject: Chemistry And Materials Science, Polymers And Plastics Keywords: Nanomedicine; molecularly imprinted polymer; drug delivery; targeting; hybrid material
Online: 29 September 2021 (14:16:32 CEST)
Molecularly imprinted polymers (MIPs) have been widely used in nanomedicine during the last few years. However, their potential is limited by their intrinsic properties resulting, for instance, in lack of control in drug release processes or complex detection for in vivo imaging. Recent attempts in creating hybrid nanomaterials combining MIPs with inorganic nanomaterials succeeded in providing a wide range of new interesting properties suitable for nanomedicine. Through this review, we aim to illustrate how hybrids molecularly imprinted polymers may improve patient care with enhanced imaging, treatments and combination of both.
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: galangin; Self microemulsion drug delivery system; Antioxidant damage; Pharmacokinetics
Online: 15 June 2021 (15:30:12 CEST)
Galangin(Gal) is a natural active flavonoid compound separated from the roots and rhizomes of Alpinia ofcinarum Hance. Modern pharmacological studies have shown that Gal has a variety of biological activities such as anti-tumor, anti-fungal, anti-bacterial, anti-inflammatory, anti-ischemic stroke, suppressing vitiligo and Alzheimer’s disease, etc. The purpose of this research was to prepare a galangin self-microemulsion drug delivery system (Gal-SMEDDS) and compare its anti-oxidant activity and pharmacokinetics with free Gal.The average particle size of the prepared Gal-SMEDDS was approximately 21.33 nm, the polydispersity index was 0.096, the zeta potential was -4.09 mV, and the entrapment efficiency was 96.74%. Compared with free Gal, the release of Gal-SMEDDS was improved in vitro release experiment. Cell experiments showed that Gal had obvious anti-oxidation effect, and the effect of Gal-SMEDDS was better than that of free Gal. In vivo pharmacokinetic experiments showed that the pharmacokinetic parameters of Gal-SMEDDS were better than that of free Gal, which indicated that the self-microemulsion drug delivery system(SMEDDS) effectively increases the oral bioavailability of Gal and alters its pharmacokinetic parameters, such that it may be effective in the treatment of anti-oxidant.
ARTICLE | doi:10.20944/preprints202104.0047.v2
Subject: Chemistry And Materials Science, Biomaterials Keywords: Hydrogels; Sodium alginate; Betamethasone; Drug delivery; Cartilage tissue engineering
Online: 6 April 2021 (10:03:04 CEST)
Hydrogels obtained from the combination of different polymers are an interesting strategy for the development of controlled release system platforms and tissue engineering scaffolds. In this study, the applicability of sodium alginate-g-(QCL-co-HEMA) hydrogels for these biomedical applications was evaluated. Hydrogels were synthesized by free-radical polymerization using different concentration of the components. The hydrogels were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, and swelling degree; betamethasone release as well as the in vitro cytocompatibility with chondrocytes and fibroblast cells were also evaluated. Scanning electron microscopy confirmed the porous surface morphology of the hydrogels in all cases. The swelling percent was determined at different pH and was observed to be pH-sensitive. The controlled release behavior of betamethasone from the matrices was investigated in PBS media (pH = 7.4) and the drug was released in a controlled manner up to 8 h. Human chondrocytes and fibroblasts were cultured on the hydrogels. The MTS assay shown that almost all hydrogels are cytocompatibles and an increase the proliferation in both cell types after one week of incubation was observed by Live/Dead® assay. These results demonstrate that these hydrogels are attractive materials for pharmaceutical and biomedical applications due to their characteristics, their release kinetics and biocompatibility.
ARTICLE | doi:10.20944/preprints202103.0179.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: RNA interference; dsRNA delivery; small RNA production; dsRNA formulation
Online: 5 March 2021 (10:01:04 CET)
Plant pathogenic fungi are the largest group of disease-causing agents on crop plants and represent a persistent and significant threat to agriculture worldwide. Conventional approaches based on the use of pesticides raise social concern for the impact on the environment and human health and alternative control methods are urgently needed. The rapid improvement and extensive implementation of RNAi technology for various model and non-model organisms has provided the initial framework to adapt this post-transcriptional gene silencing technology for the management of fungal pathogens. In this review, we describe exogenous RNAi involved in plant pathogenic fungi and discuss small RNA production, formulation, and RNAi delivery methods. We explore some challenges with possible solutions. Furthermore, exogenous RNAi holds great potential for RNAi-mediated plant pathogenic fungal disease control.
ARTICLE | doi:10.20944/preprints202101.0505.v1
Subject: Business, Economics And Management, Accounting And Taxation Keywords: Government; Citizen; Service Delivery; Integrated Statistical Management; Registration; Information
Online: 25 January 2021 (14:48:14 CET)
Statistical management policy and system plays significant role in development of any nation as it guides the planner to analyze the gaps, design programs and allocate budget in efficient manner. Globally, design and usage of statistical management system varies relying on country specific ability and resources availability. Government of Nepal has been managing database in individual as well as thematic manner. Policy wise, thematic database is in operation based on Statistics Act 1958 and individual database is in operation based on Birth, Death and Other Personal Related Events Registration Act 1976. Though civil registration related policies have been either updated or newly formed, sectoral statistic management related policy has not been updated since its first promulgation period (1958). With no policy supporting the consolidated statistical management system, government as well as non-government agencies has been investing millions of dollars annually to collect, compile and analyze individual related data and fulfill their respective objectives. It has forced the government services and performance to be paper-based, time-consuming and tedious thus creating dis-trust among citizen each passing day. Though, formulation of legal instrument promoted digital movement and mandated shift towards e-government modality, the process has been low. Theoretically, Technology Acceptance Model (TAM) state the need of having advanced and efficient technology to be in place in current setting to improve governance, efficiency, accountability, transparency and trust. Also, the same theory state the requirement of strong willingness and motivation from the users (government, non-government and citizen) to adopt the technology based policy and system. As the integrated statistical management policy emphasizes on technology-based system or digital system, the perspectives of Technology Acceptance Model also termed as Information System Theory aid in understanding the context, conceptualizing and addressing the needs with an establishment and implementation of digital system or technology based system. This policy paper applied the Technology Acceptance Model (TAP) to examine the underlying opportunities and challenges associated with an integrated statistical management policy. With existing gaps in existing policy, system and practice alongside an overview of opportunities and challenges, this paper recommends the need of stand-alone integrated statistical management policy to consolidate sectoral as well as civil related information through single system based on recommended policy.
ARTICLE | doi:10.20944/preprints202004.0221.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Cancer; cytochrome c; drug delivery; Lewis Lung Carcinoma; nanoprecipitation
Online: 14 April 2020 (14:27:15 CEST)
The delivery of Cytochrome c (Cyt c) to the cytosol stimulates apoptosis in cells were its release from mitochondria and apoptosis induction is inhibited. We developed a drug delivery system consisting of Cyt c nanoparticles decorated with folate-poly(ethylene glycol)-poly(lactic-co-glycolic acid)-thiol (FA-PEG-PLGA-SH) to deliver Cyt c into cancer cells and test their targeting in the Lewis Lung Carcinoma (LLC) mouse model. Cyt c-PLGA-PEG-FA nanoparticles (NPs) of 253 ± 55 and 354 ± 11 nm were obtained by Cyt c nanoprecipitation, followed by surface decoration with the co-polymer SH-PLGA-PEG-FA, and compared to a nanoparticle-free formulation. Overexpression of FA in LLC cells and internalization of Cyt c-PLGA-PEG-FA nanoparticles (NPs) was confirmed by confocal microscopy. Caspase activation assays show NPs retain 88-96% Cyt c activity. The NP formulations were more efficient in decreasing LLC cell viability than the NP-free formulation, with IC50: 49.2 to 70.1 μg/ml versus 129.5 μg/ml, respectively. Our NP system is thrice as selective towards cancerous than normal cells. In-vivo studies using tagged nanoparticles show accumulation in mouse LLC tumor 5 min post-injection. In conclusion, our NP delivery system for Cyt c shows superiority over the NP-free formulation and reaches a folic acid-overexpressing tumor in an immune-competent animal model.
ARTICLE | doi:10.20944/preprints202002.0115.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: nanodiamond; tritium; biodistribution; Ewing sarcoma; drug delivery; siRNA; nanomedicine
Online: 9 February 2020 (17:37:11 CET)
Nanodiamonds of detonation origin are promising delivery agents of anti-cancer therapeutic compounds in a whole organism like mouse, owing to their versatile surface chemistry and ultra-small 5 nm average primary size compatible with natural elimination routes. However, to date, little is known about tissue distribution, elimination pathways and efficacy of nanodiamonds-based therapy in mice. In this report, we studied the capacity of cationic hydrogenated detonation nanodiamonds to carry active small interfering RNA (siRNA) in a mice model of Ewing sarcoma, a bone cancer of young adult due in the vast majority to the EWS-Fli1 junction oncogene. Replacing hydrogen gas by its radioactive analog tritium gas led to the formation of labeled nanodiamonds and allowed us to investigate their distribution throughout mouse organs and their excretion in urine and feces. We also demonstrated that siRNA directed against EWS-Fli1 inhibited this oncogene expression in tumor xenografted on mice. This work is a significant step to establish cationic hydrogenated detonation nanodiamond as an effective agent for in vivo delivery of active siRNA.
ARTICLE | doi:10.20944/preprints201810.0515.v1
Subject: Chemistry And Materials Science, Polymers And Plastics Keywords: polymeric amines; oligonucleotides; critical length; grafted polyamines; gene delivery
Online: 23 October 2018 (04:16:11 CEST)
Amine containing polymers are extensively studied as special carriers for short-chain RNA (13–25 nucleotides) which are applied as gene silencing agent in gene therapy of various diseases including cancer. Elaboration of the oligonucleotide carriers requires knowledge about peculiarities of oligonucleotide - polymeric amine interaction. Critical length of the interacting chains is the important parameter which allows to design sophisticated constructions containing oligonucleotide binding segments, solubilizing, protective and aiming parts. We studied interaction of (TCAG)n, n=1-6 DNA oligonucleotides with polyethylenimine and poly(N-(3-((3-(dimethylamino)propyl)(methyl)amino)propyl)-N-methylacrylamide). Critical length for oligonucleotides in interaction with polymeric amines is 8-12 units and complexation at these length can be accompanied by "all-or-nothing" effects. New dimethylacrylamide based polymers with grafted polyamine chains were obtained and studied in complexation with DNA and RNA oligonucleotides. The most effective interaction and transfection activity into A549 cancer cells was found for a sample with average number of nitrogens in polyamine chain equal to 27, i.e. for a sample in which all grafted chains are longer the critical length for polymeric amine - oligonucleotide complexation.
REVIEW | doi:10.20944/preprints201808.0210.v1
Subject: Chemistry And Materials Science, Nanotechnology Keywords: microbubbles; nanobubbles; photoacoustic imaging; ultrasonic imaging; ROS; oxygen delivery
Online: 11 August 2018 (18:49:18 CEST)
Microbubbles and nanobubbles can be prepared using various shells, such as phospholipids, polymers, proteins, and surfactants. They are echogenic and can be used as contrast agents for ultrasonic and photoacoustic imaging. These bubbles can be engineered in various sizes as vehicles for gas and drug delivery applications with novel properties and flexible structures. Hypoxic areas in tumors develop owing to an imbalance of oxygen supply and demand. In tumors, hypoxic regions have shown more resistance to chemotherapy, radiotherapy, and photodynamic therapies. The efficacy of photodynamic therapy depends on the availability of oxygen in the tumor to generate reactive oxygen species. Micro/nanobubbles have been shown to reverse hypoxic conditions and increase tissue oxygen levels. This review summarizes the synthesis methods and shell compositions of micro/nanobubbles and methods deployed for oxygen delivery. In addition, the shortcomings and prospects of engineering micro/nanobubbles are discussed for their potential use in photodynamic therapy.
REVIEW | doi:10.20944/preprints201807.0226.v1
Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: galvanic replacement; photothermal therapy; drug delivery; nanoparticles; cancer treatment
Online: 13 July 2018 (05:11:21 CEST)
Owing to their unique physicochemical properties, nanoparticles are used in a variety of ways in the field of cancer treatment, including imaging, drug delivery, and photothermal and photodynamic therapies. The fascinating properties of nanoparticles are determined by their size, morphology, and constituent elements, and various synthetic methods and post-synthetic techniques have been applied to control these factors. Herein, we present examples of shape and composition control through galvanic replacement, a technique that exploits redox potential differences between elements to induce spontaneous ion-exchange and highlight its specific contributions to cancer treatment applications. The present article identifies the recent advances in nanoparticle formation techniques and discusses the future outlook of the field.
ARTICLE | doi:10.20944/preprints201608.0199.v1
Subject: Biology And Life Sciences, Aging Keywords: active ageing; social participation; mobility; assistive technologies; service delivery
Online: 23 August 2016 (14:53:52 CEST)
Active ageing is defined as the process of optimizing opportunities for physical, social and mental health to enable older people to take an active part in society without discrimination and to enjoy an independent and good quality of life. The World Health Organization assumed this as a process for increasing and maintaining an individual’s participation in activities to enhance his/her quality of life. In this survey, the authors addressed the following question: “Is assistive technology (AT) for mobility contributing to enhancement of lifelong capacity and performance?”. From June 2015 until February 2016, 96 community dwelling adults, AT users for mobility (powered wheelchairs, manual wheelchairs, lower limb prostheses, walkers, crutches and canes), aged 45-97, mean 67.02 +/- 14.24 years old, 56.3% female, were interviewed using the Psychosocial Impact of Assistive Devices Scale (P-PIADS), the Activities and Participation Profile related to Mobility (APPM) and demographics, clinical and questions about AT use and training. The participants’ profiles revealed moderate limitation and restrictions in participation, measured by the APPM (2.03). Most participants showed positive impact of AT; average scores obtained from the P-PIADS subscales were: Self-esteem 0.62, Competency 1.11 and Adaptability 1.10. P-PIADS total was 0.96, with the powered wheelchair users scoring the highest (1.53) and the walker users scoring the lowest (0.73). All subscales and P-PIADS total were positively correlated with the activities and participation profile. There was no relation between age and the psychosocial impact of AT or activities and participation profile. These results encourage the authors to follow these participants up for a lifelong intervention. To accomplish that aim, currently, the protocol is implemented at the AT prescribing centers in Coimbra, Portugal in order to assess the impact of AT on participation in society, one of the domains of the Active Ageing Index, a new analytical tool to help policy makers in developing policies for active and healthy ageing.
REVIEW | doi:10.20944/preprints202310.1434.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: carbon nanodots (CNDs); cannabidiol (CBD); drug delivery; encapsulation; bioavailability; adsorption
Online: 23 October 2023 (11:12:37 CEST)
The dynamic interaction between carbon nanodots (CNDs) and cannabidiol (CBD) has captured significant attention as an innovative avenue for redefining drug delivery and amplifying therapeutic effectiveness. This in-depth review delves into the intricate synergy between these two elements, unveiling their profound potential in medicine. Commencing with an examination of the unique characteristics of CNDs and the techniques governing their synthesis, we discuss their versatility as drug carriers, highlighting their invaluable role in advancing CBD delivery. Cannabidiol, a non-psychoactive compound sourced from cannabis, has emerged as a focal point for its diverse therapeutic attributes. Nevertheless, the limitations posed by its restricted bioavailability and susceptibility to degradation pose substantial hindrances to realizing its full potential. Here, we elucidate how the amalgamation of CBD with CNDs transcends these challenges. We delve into the mechanisms that underlie this synergy, such as the augmentation of solubility and the safeguarding of CBD against premature breakdown, providing an intricate analysis. We will also journey you through a comprehensive exploration of diverse CBD loading techniques onto CNDs, dissecting the realms of physical encapsulation, covalent bonding, and adsorption processes. In summation, the combination of CNDs and CBD presents an extraordinary opportunity to elevate therapeutic outcomes. This synergetic paradigm masterfully tackles pivotal challenges in drug delivery, thereby paving the path for pioneering medical solutions.
REVIEW | doi:10.20944/preprints202310.1097.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Nanobodies; respiratory viral infections; spray and aerosol particles; targeted delivery.
Online: 18 October 2023 (03:04:54 CEST)
Respiratory viral infections, including influenza, respiratory syncytial virus (RSV), and, more recently, the coronavirus disease 2019 (COVID-19) pandemic, continue to pose significant global health threats. Conventional treatments for these infections often face challenges such as limited efficacy, the emergence of drug-resistant strains, and the requirement for frequent administration. In recent years, nanobodies have emerged as a promising class of therapeutic agents due to their unique properties, including small size, high stability, and specific binding capabilities. This mini-review article focuses on the application of nanobodies as spray and aerosol particles for the treatment of respiratory viral infections. Furthermore, we highlight the remarkable efficacy of nanobodies in preclinical and clinical studies against respiratory viruses, including their ability to neutralize viral particles, inhibit viral replication, and modulate the host immune response. We discuss the potential advantages of using nanobodies as inhalable formulations, including their improved delivery to the respiratory tract, enhanced stability in aerosol form, and reduced systemic side effects. Additionally, we explore the various strategies employed to engineer nanobodies for optimal aerosol delivery, such as conjugation to carrier particles or formulation as dry powders. We also examine the potential challenges and limitations associated with the development of nanobody-based aerosol therapies, including production scalability, cost-effectiveness, and regulatory considerations.
REVIEW | doi:10.20944/preprints202309.0616.v1
Subject: Chemistry And Materials Science, Food Chemistry Keywords: Anthocyanins; immune cells; gut microbiota; bioavailability; efficacy; nano-delivery methods.
Online: 11 September 2023 (09:36:47 CEST)
Anthocyanins (ACNs) have attracted considerable attention for their potential to modulate the immune system. Research has revealed their antioxidant and anti-inflammatory properties, which play a crucial role in immune regulation by influencing key immune cells such as lymphocytes, macrophages, and dendritic cells. Moreover, ACNs contribute to maintaining a balance between proinflammatory and anti-inflammatory cytokines, thus promoting immune health. Beyond their direct effects on immune cells, ACNs significantly impact gut health and the microbiota, essential factors in immune regulation. Emerging evidence suggests that they positively influence the composition of the gut microbiome that enhance the immunomodulatory effects of ACNs. Furthermore, these compounds synergize with other bioactive substances, such as vitamins and minerals, further enhancing their potential as immune-supporting dietary supplements. However, detailed clinical studies must fully validate these findings and determine safe dosages for different populations. Incorporating these natural compounds into functional foods or supplements can revolutionize the management of immune-related conditions. Personalized nutrition and healthcare strategies can be developed to enhance overall well-being and immune resilience by fully understanding the mechanisms underlying their actions. Recent advancements in delivery methods have focused on improving the bioavailability and effectiveness of ACNs, providing promising avenues for future applications.
ARTICLE | doi:10.20944/preprints202308.2153.v1
Subject: Medicine And Pharmacology, Pharmacy Keywords: Hydrogel gatekeeper; mesoporous silica nanoparticles; stimuli-sensitive delivery; chemotherapy; doxorubicin
Online: 31 August 2023 (12:35:42 CEST)
Hydrogels can offer many opportunities for drug delivery strategies. They can be used on their own or their benefits can be further exploited in combination with other nanocarriers. Intelligent hydrogels that react to changes in the surrounding environment can be utilized as gatekeepers and provide sustained on demand drug release. In this study, a hybrid nanosystem for tempera-ture and pH sensitive delivery was prepared from MCM-41 nanoparticles grafted with newly synthesized thermosensitive hydrogel (MCM-41/AA-g-PnVCL). The initial particles were chemi-cally modified by carboxyl groups attachment. Later, they were grafted with agar (AA) and vi-nylcaprolactam (VCL) by free radical polymerization. Doxorubicin was applied as a model hy-drophilic chemotherapeutic drug. The successful formulation was confirmed by FT-IR and TGA. Transmission electron microscopy and dynamic light scattering analysis showed small particles with negative zeta potential. Their release behaviour was investigated in vitro in different pH media and at different temperatures. At tumor simulating conditions (40ºC and pH 4.0) doxoru-bicin was almost completely released within 72 hours. The biocompatibility of the proposed na-noparticles was demonstrated by in vitro haemolysis assay. These results suggest the possible parenteral application of the newly prepared hydrogel-functionalized mesoporous silica nanopar-ticles for temperature-sensitive and pH-triggered drug delivery at the tumor site.
ARTICLE | doi:10.20944/preprints202308.1558.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: glioblastoma; intranasal delivery; oncolytic adenovirus; XVir‐N‐31; shuttle cells
Online: 22 August 2023 (11:22:58 CEST)
Glioblastoma (GBM) is an aggressive and lethal primary brain tumor with restricted treatment options and a dismal prognosis. Oncolytic virotherapy (OV) has developed as a promising approach for GBM treatment. However, reaching invasive GBM cells may be hindered by tumor-surrounding, non-neoplastic cells when the OV is applied intratumorally. In this study, using a rodent GBM model and immunofluorescence analyses, we investigated the intranasal delivery of the oncolytic adenovirus (OAV) XVir-N-31 via virus-loaded, optimized shuttle cells. Intranasal administration (INA) was selected due to its non-invasive nature and the potential to bypass the blood-brain barrier (BBB). Our findings demonstrate that INA of XVir-N-31 loaded shuttle cells successfully delivers OAVs to the core tumor and invasive GBM cells, significantly prolongs the survival of GBM bearing mice, induces immunogenic cell death and finally reduces tumor burden, all this highlighting the therapeutic potential of this innovative approach. Overall, this study provides compelling evidence for the effectiveness of INA of XVir-N-31 via shuttle cells as a promising therapeutic strategy for GBM. The non-invasive nature of INA of OV-loaded shuttle cells holds great promise for future clinical translation. However, further research is required to assess the efficacy of this approach to ultimately progress in human clinical trials.
ARTICLE | doi:10.20944/preprints202308.1057.v1
Subject: Chemistry And Materials Science, Polymers And Plastics Keywords: Targeted delivery; A6 peptide; PCL-PEG; Nanoparticle; Nanopolymer; Curcumin; Cancer
Online: 14 August 2023 (15:36:50 CEST)
Polymeric based nanoparticles are garnering significant interest for their potential in drug delivery. Specially, nanopolymers that have been functionalized with molecules, such as proteins or peptides, are a versatile vehicle for drug delivery. Curcumin (Cur) is one of the most commonly studied anticancer compounds and is widely acknowledged as having positive effects on human health. However, its insolubility and low bio-distribution greatly hinder the exploitation of its beneficial traits. In this study, our team created a nano delivery system which utilized a nanopolymer called PCL-PEG (poly(ε-caprolactone)-poly (ethylene glycol)). This system was functionalized with A6 peptide to enable targeted delivery of Cur. The system was designed with advantageous nanoparticles (NPs), including a stable zeta potential (–32.7), small size (54.3), uniform surface morphology, and high hydrophilicity (13.72°). In addition, targeted delivery systems exhibited high encapsulation efficacy (93 ± 0.89 %), and drug loading (16.7 ± 0.9 %), and were characterized by a slow and gradual release profile with a release of approximately 83.13 ± 0.12%. The MTT assay results showed that the formulation known as Cur-NPs-A6 caused a significant increase in cell death in MDA-MB-231 cancer cells (IC50 = 23.31 ± 0.85 µM). The designed delivery system did not cause any harm to the noncancerous MCF-10A cells (normal group). Furthermore, the results of both the RT-qPCR and invasion assays demonstrated that the designed system was able to effectively activate the apoptosis pathway and inhibit cell invasion. Our findings suggest that the use of the designed smart delivery system, which is functionalized with A6 peptide that has a high affinity for CD44 receptor - known to be upregulated in numerous malignant conditions, could be a highly efficient approach to treating cancer.