In recent years, the delivery of medical supplies has faced significant challenges due to natural disasters and recurrent public health emergencies. Addressing the need for improved logistics operations during such crises, this article presents an innovative approach integrating vehicle and Unmanned Aerial Vehicle (UAV) logistics to enhance the efficiency and resilience of medical supply chains. Our study introduces a dual-mode distribution framework that employs the Density-Based Spatial Clustering of Applications with Noise (DBSCAN) algorithm for efficiently clustering demand zones unreachable by conventional vehicles, thereby identifying areas requiring UAV delivery. Furthermore, we categorize the demand for medical supplies into two distinct sets based on vehicle accessibility, optimizing distribution routes via both UAVs and vehicles. Through comparative analysis, our findings reveal that the artificial bee colony (ABC) algorithm significantly outperforms the genetic algorithm in terms of solving efficiency, iteration counts, and delivery speed. However, the ABC algorithm's tendency towards early local optimization and rapid convergence leads to potential stagnation in local optima. To mitigate this issue, we incorporate a simulated annealing technique into the ABC framework, culminating in a refined optimization approach that successfully overcomes the limitations of premature local optima convergence. The experimental results validate the efficacy of our enhanced algorithm, demonstrating reduced iteration counts, shorter computation times, and substantially improved solution quality over traditional logistic models. The proposed method holds promise for significantly improving the operational efficiency and service quality of the healthcare system's logistics during critical situations.

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[30]-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.

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

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.

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.

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.

Glioblastoma (GBM) is a prevalent type of malignancy within the central nervous system (CNS), associated with a poor prognosis. The standard treatment for GBM includes surgical resection of the tumor, followed by radiotherapy and chemotherapy; yet despite these interventions, overall treatment outcomes remain suboptimal. The blood-brain barrier (BBB), which plays a crucial role in maintaining the stability of brain tissue under normal physiological conditions of the CNS,also poses a significant obstacle to the effective delivery of therapeutic agents to GBM. Recent preclinical studies have demonstrated that nanomedicine delivery systems (NDDS) offer promising results, demonstrating both effective GBM targeting and safety, thereby presenting a potential solution for targeted drug delivery. This review explores the various strategies employed in preclinical studies to overcome the BBB for drug delivery. Subsequently, the results of clinical translation of NDDS has been summarized, highlighting the progress made. Finally, we discuss potential strategies for advancing NDDS development and accelerating their translational research through well-designed clinical trials in GBM therapy.

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.

Significant advancements have been made in controlled drug delivery systems in recent years, especially for oral administration. Conventional methods, although groundbreaking, encounter significant constraints when handling drugs with weak acidity or alkalinity because of their solubility being influenced by pH. The release rates of these ionizable drugs are subject to variability, which is influenced by factors such as the pH of the gastrointestinal tract (GIT), patient-specific conditions, and whether the patient is in a fed or fasted state. As a result, there is often a lack of correlation between in vitro and in vivo data. Therefore, it is imperative to develop drug delivery systems that are not affected by changes in pH in order to address these limitations. This review delves into different strategies that have been developed to achieve drug release that is not affected by changes in pH. These strategies include the utilisation of Diffucaps technology, the incorporation of pH modifiers and surfactants, the combination of non-ionic and ionic polymers, the implementation of supersaturating techniques with nucleation inhibitors, and the utilisation of osmotic drug delivery systems. We assess the efficacy of these methods in reducing the influence of pH fluctuations on the solubility and release rates of drugs. In addition, we explore the potential of these innovative techniques to enhance the reliability and predictability of drug delivery, ultimately leading to better therapeutic results. This review provides an in-depth information of various pH independent controlled drug delivery based formulation and By summarizing the existing technologies and looking into the future, the importance of innovation in pH independent delivery systems is emphasised, laying a good foundation for the future design of simple drug delivery systems, which will be conducive to achieving a wider range of applications in oral drug delivery system.

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.

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.

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.

The e-commerce sector is in a constant state of growth and evolution, particularly within its subdomain of online food delivery. As such, ensuring customer satisfaction is critical for companies working in this field. One way to achieve this is by providing accurate delivery time estimation. While companies can track couriers via GPS, they often lack real-time data on traffic and road conditions, complicating delivery time predictions. To address this, a range of statistical and machine learning techniques are being employed, including neural networks and specialized expert systems, with different degree of success. One issue with neural networks and machine learning models is their heavy dependence on vast, high quality data. To mitigate this issue we propose two Bayesian generalized linear models to predict time of the delivery. Utilizing a linear combination of predictor variables, we generate practical range of outputs with Hamiltonian Monte Carlo sampling method. These models offer a balance of generality and adaptability, allowing for tuning with expert knowledge. They were compared with PSIS-LOO and WAIC criteria. Results show that both models accurately estimated delivery times from the dataset, while maintaining numerical stability. Model with more predictor variables proved to be more accurate.

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.

Hypertension (HTN) is the foremost contributor to cardiovascular diseases (CVD), which remain a leading cause of death. However, adherence to the properly prescribed dosage form is critical and challenging for patients with chronic diseases such as HTN to prevent illness progression and death. The study’s objective was to develop AMB-loaded subcutaneous implants to reduce the frequency of administration, thus improving patient compliance during HTN management. AMB subcutaneous implants were prepared using continuous hot melt extrusion technology using PCL and PLGA with dimensions of 7.5 cm (length) by 2 mm (diameter). The implants were characterized for thermal characteristics, drug-excipient incompatibilities, surface morphology, fracturability, in vitro release, and stability studies. DSC showed that the drug was in the crystalline state in the fabricated implants. Scanning Electron Microscopy (SEM) revealed a smooth surface. The lead formulation presented good drug content, showed an extended drug release profile over 30 days, and followed zero-order release kinetics with a mean dissolution time of 15 days. The formulation was stable over 30 days in accelerated stability conditions (the last time point was tested, 40℃/75% RH), and the release profile was similar to the initial drug release profile. The lead formulation showed good fracturability during textural analysis. Therefore, the hot melt extruded implants could be an alternative management strategy for conventional amlodipine besylate (AMB) formulation.

Interleukin-12 (IL-12) is considered to be a promising cytokine for enhancing anti-tumor immune response. However, recombinant IL-12 had significant toxicity and limited efficacy in early clinical trials. Recently, many strategies for delivering IL-12 to tumor tissues have been developed, such as modifying IL-12, utilizing viral vectors, non-viral vectors and cellular vectors. Previous studies have found that IL-12 fusion with extracellular matrix proteins, collagen and immune factors is a way to enhance its therapeutic potential. In addition, studies have demonstrated that viral vectors are a good platform, and a variety of viruses such as oncolytic viruses, adenoviruses and poxviruses have been used to deliver IL-12, and testing has been conducted in various cancer models. Local expression of IL-12 in tumors based on viral delivery avoids systemic toxicity while inducing effective anti-tumor immunity and acting synergistically with other therapies without compromising safety. Also, lipid nanoparticles are currently considered to be the most mature drug delivery system. Moreover, cells are also considered to be drug carriers because they can effectively deliver therapeutic substances to tumors. In this article, we will systematically discuss the antitumor effects of IL-12 on its own or in combination with other therapies based on different delivery strategies.

Hamman’s syndrome is a rare condition that mostly affects young males, often with a predisposition of asthma. It includes the presence of free air in the mediastinum and subcutaneous emfysema with no other underlying cause such as trauma or infection. It occurs spontanously and often in association with prolonged valsalva manouvre. This might explain why there are some cases of Hamman syndrome among young females giving birth. Here we present a case report of a 24-year- old primigravida with Hamman’s syndrome. She presented with symptoms a few hours after an uncomplicated vaginal delivery at 40+1 pregnancy week. The symptoms resolved spontanously after a few days of observation. We also give a systemic review of reported cases since 2000 to provide overview on pathomechanism, symptoms, diagnostics, treatment and management of this condition. Hamman’s syndrome is a rare, usually benign, but potentially serious complication that can occur during the second stage of labour. Diagnostics include inquiring about typical symptoms, clinical examination and chest x-ray or CT scan. Treatment is usually conservative with oxygen, bronchodilators and pain relief. The reccurence rate is low and there is no contraindication to vaginal delivery in future pregnancies. However, it is suggested that physicians and midwives be cautious and consider low threshold for instrumental delivery or caesarean section to avoid excessive valsalva manoeuvre.

Melatonin is a ubiquitous molecule found in living organisms, ranging from bacteria to plants and mammals. It possesses various properties, partly due to its robust antioxidant nature and partly owed to its specific interaction with melatonin receptors present in almost all tissues. Melatonin regulates different physiological functions and contributes to the homeostasis of the entire organism. In the human eye, a small amount of melatonin is also present, produced by cells in the anterior segment and the posterior pole, including the retina. In the eye, melatonin may provide antioxidant protection along with regulating physiological functions of ocular tissues, including intraocular pressure (IOP). Therefore, it is conceivable that the exogenous administration of sufficiently high amounts of melatonin to the eye could be beneficial in several instances: for the treatment of eye pathologies like glaucoma, due to the IOP-lowering and neuroprotection effects of melatonin; for the prevention of other dysfunctions, such as dry eye and refractive defects (cataract and myopia) mainly due to its antioxidant properties; for diabetic retinopathy due to its metabolic influence and neuroprotective effects; for macular degeneration due to the antioxidant and neuroprotective properties; and for uveitis, mostly owing to anti-inflammatory and immunomodulatory properties. This paper reviews the scientific evidence supporting the use of melatonin in different ocular districts and provides data suggesting that the topical administration of melatonin as eye drops is a real possibility. This way, its distribution and concentration in different ocular tissues may support its pleiotropic therapeutic effects.

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

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.

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.

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.

Abstract: Lipidic carriers employed for the entrapment, encapsulation and precise targeting the bioactive compounds offer significant advantages to the biomedical, pharmaceutical, nutraceutical and cosmeceutical industries. These lipid and phospholipid-based vesicles can improve the solubility, permeation, pharmacokinetics, pharmacodynamics and bioavailability of the encapsulated material. As a matter of fact, nano-sized phospholipid vesicles have attained the highest success rate in commercialization among the available drug encapsulation technologies. Nevertheless, developing industrially acceptable products still remains a challenge. Among the main disadvantages of conventional lipidic carriers are their instability in the biological environments, and their sensitivity to changes in the pH, temperature and enzymes. To overcome these problems, the new generation of phospho/lipid-based carrier systems was developed using ingredients from microorganisms living in extremely harsh environments (i.e., archeaeobacteria). The present entry aims to review unique features of archaeolipids and recent developments in their application for the encapsulation of genetic material as well as their role and function as adjuvants and vaccine candidates.

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.

The COVID-19 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is in its 5th year and is being maintained by the inability of current spike-alone based COVID-19 vaccines to prevent transmission leading to the continuous emergence of variants and sub-variants of concern (VOCs). This underscores the critical need for next-generation broad-spectrum pan-Coronavirus vaccines (pan-CoV vaccine) to break this cycle and end the pandemic. The development of a pan-CoV vaccine offering protection against a wide array of VOCs requires two key elements: (1) identifying protective antigens that are highly conserved between passed, current and future VOCs; and (2) developing a safe and efficient antigens deliver system for induction of broad-based B- and T-cell immunity. This review will (1) present the current state of antigen delivery platforms involving a multifaceted approach, including bioinformatics, molecular and structural biology, immunology, and advanced computational methods; (2) discuss the challenges facing development of safe and effective antigen delivery platforms; and (3) highlight the potential of nucleoside-modified mRNA encapsulated in lipid nanoparticles (LNP) as the platform that is well suited to the needs of a next-generation pan-CoV vaccine, such as the ability to induce broad-based immunity and amenable to large-scale manufacturing to safely provide durable protective immunity against current and future Coronavirus threats.

The skin, being the largest organ of the human body, serves as the primary barrier against external insults, including UV radiation, pollutants, and microbial pathogens. However, prolonged exposure to these environmental stressors can lead to the generation of reactive oxygen species (ROS), causing oxidative stress, inflammation, and ultimately, skin aging and diseases. Antioxidants play a crucial role in neutralizing ROS and preserving skin health by preventing oxidative damage. In recent years, nanotechnology has emerged as a powerful tool for enhancing the delivery of an-tioxidants onto the skin. In particular, liposomal formulations have offered unique advantages such as improved stability, controlled release, and enhanced penetration through the skin barrier. This has led to a surge in research focused on developing liposomal-based antioxidant delivery systems tailored for skin health applications. Through a comprehensive analysis of the literature from the 2019-2024 period, this review provides an overview of emerging trends in the use of liposomal delivery systems developed for antioxidants aimed at improving skin health. It explores the latest advancements in liposomal formulation strategies, vesicles characterization and their applications in delivering antioxidants to combat oxidative stress-induced skin damage and other associated skin pathologies.

This article mainly discusses the prospects of DNA vaccines as a future form of immunization. DNA vaccines, also known as nucleic acid vaccines or gene vaccines, inject genes encoding specific protein antigens directly into animals. By utilizing recombinant eukaryotic expression vectors, they activate the immune system to produce specific humoral and cellular immune responses, providing comprehensive protection against specific pathogens. Compared with traditional vaccines, DNA vaccines have shown new promise in addressing many viral infections. Although no DNA vaccines have been approved for use in humans at present, research on DNA vaccines for specific human diseases, such as prostate cancer, is ongoing. Additionally, the delivery methods of DNA vaccines, including oral vaccines and particle-mediated epidermal vaccination, as well as the challenges and directions for improvement in their clinical application, are explored. Finally, despite these challenges, the research and application prospects of DNA vaccines are broad.

Polycystic ovary syndrome (PCOS) is the predominant endocrine disorder among women of re-productive age and represents the leading cause of anovulatory infertility, which imposes a con-siderable health and economic burden. Currently, medications used to treat PCOS can lead to certain adverse reactions, such as affecting fertility and increasing the risk of venous thrombosis. Drug delivery systems utilizing nanomaterials, characterized by prolonged half-life, preci-sion-targeted delivery, enhanced bioavailability, and reduced toxicity, are currently being em-ployed in the management of PCOS. This innovative approach is gaining traction as a favored strategy for augmenting the therapeutic efficacy of medications. Consequently, this paper dis-cusses the roles of nanoparticles, nanocarriers, and targeted ligands within nanomaterial-based drug delivery systems, aiming to identify optimal methodologies for treating PCOS using nano-materials. Additionally, prospective research avenues concerning nanomaterial-based delivery systems in the context of PCOS, as well as the implications of existing insights on the advancement of novel therapies for PCOS, are highlighted.

Extracellular vesicles (EVs) are natural carriers of biomolecules that play a crucial role in cell-to-cell communication and tissue homeostasis under normal and pathological conditions, including inflammatory diseases and cancer. Since the discovery of the pro-regenerative and immune-modulating properties of EVs, EV-based therapeutics have entered clinical trials for conditions such as myocardial infarction and autoimmune diseases, among others. Due to their unique advantages—such as superior bioavailability, substantial packaging capacity, and the ability to traverse biological barriers—EVs are regarded as a promising platform for targeted drug delivery. However, achieving sufficient accumulation of therapeutic agents at the target site necessitates a larger quantity of EVs per dose compared to using EVs as standalone drugs. This challenge can be addressed by administering larger doses of EVs, increasing the drug dosage per administration, or enhancing the selective accumulation of EVs at target cells. In this review, we will discuss methods to improve the isolation and purification of EVs, approaches to enhance cargo packaging—including proteins, RNAs, and small-molecule drugs—and technologies for displaying targeting ligands on the surface of EVs to facilitate improved targeting. Ultimately, this guide can be applied to the development of novel classes of EV-based therapeutics and to overcoming existing technological challenges.

As the world population grows, fulfilling the need for biomaterials in the healthcare system becomes increasingly important. Biomaterials, which include metals, polymers, ceramics, and composites, play an important role in the creation of medical devices that improve people's lives. The European Society for Biomaterials described biomaterials as non-biological materials used in medical devices to interact with biological systems. This definition has developed to encompass materials that treat, assess, or replace tissues or bodily functions. Biocompatibility, as defined by the FDA, is a key feature of biomaterials, as is the requirement to fulfil design requirements such as mechanical performance, geometry, and electrical control. Over the last decade, advances in regenerative medicine and tissue engineering have boosted biomaterials' usage in medical applications dramatically. Despite its promise, scientists, engineers, and physicians continue to face significant challenges due to the complexity of biomaterials. Biomaterials have various benefits, including biodegradability, non-toxicity, and biocompatibility, making them extremely useful for replacing, sustaining, or improving biological activities in damaged tissues. They are used in a wide range of applications, including tissue engineering implants, human tissue healing and regeneration, medication delivery systems, and biosensors. This study gives insights into the fundamental characteristics, case studies, and ethical issues associated with the usage and use of biomaterials, further examining their potential and significance in healthcare and medicine.

Cancer is a highly heterogeneous disease and remains a global health challenge affecting millions of human lives worldwide. Despite advancements in conventional treatments like surgery, chemotherapy, and immunotherapy, the rise of multidrug resistance, tumor recurrence, and severe side effects necessitates innovative therapeutic approaches. The complex nature of the tumor microenvironment (TME) further compromises the efficacy of traditional chemotherapy drugs. Recently, stimulus-responsive nanomedicines designed to target TME characteristics (e.g., pH, redox, enzymes) have gained attention for their potential to enhance anticancer efficacy while minimizing adverse effects. Among various nanocarriers, hydrogels are an interesting class of nanocarriers used in cancer therapy due to their high water content, adjustable mechanical characteristics, and ability to respond to external/internal stimuli. These properties make hydrogels an ideal nanocarrier for controlled drug release within the TME. This review comprehensively surveys the latest advancements in stimulus-responsive hydrogels for cancer therapy, exploring various stimuli-responsive mechanisms, including biological (e.g., pH, redox), chemical (e.g., enzymes, glucose), and physical (e.g., temperature, light), as well as dual- or multi-stimuli responsiveness. This review will offer novel perspectives on the development of stimulus-responsive hydrogels for cancer therapy.

Skin inflammation associated with chronic diseases has the direct action of keratinocytes in its immunopathogenesis, leading to a series of immune responses. However, there are still no highly targeted treatments, and the development of more specific therapies is highly desirable. In the present work, nanocapsules containing quinizarin (QZ/NC) were developed, evaluating their act in a model of the keratinocytes inflammatory process in vitro with the action of Photodynamic Therapy, analyzing the permeation in a 3D skin model. Physicochemical, stability, cytotoxicity and permeation analyses of the nanomaterials were carried out. The nanocapsules showed desirable physicochemical characteristics and were stable during the analysis period, without spectroscopic modifications. The cell viability test carried out showed no cytotoxicity at the lowest QZ/NC concentrations. The permeation and cellular uptake studies showed the permeation of QZ/NC in 3D skin models and the intracellular incorporation and internalization of the drug, enhancing its action in the drug delivery technique. Promising results were presented using the model developed to induce the inflammatory process in vitro and applying the synthesized nanomaterial in conjunction with PDT, where a decrease in the levels of cytokines analyzed was observed, representing a possible new therapeutic approach for inflammatory skin diseases.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Bioavailability, release and stability of pharmaceuticals under physicochemical conditions is the major cause of drug candidates failing during their clinical trials. Therefore, extensive efforts have been invested in the development of novel drug delivery systems able to transport drugs to a desired site and to improve the bioavailability. Hydrogels, and peptide hydrogels in particular, have been extensively investigated due to their excellent biocompatibility and biodegradability properties. However, peptide hydrogels often have weak mechanical strength, which limits their therapeutic efficacy. Therefore, a number of methods in improving their rheological properties have been established. This review will cover the broad area of drug delivery focusing on the recent developments in this research field. We will discuss the variety of different types of nanocarrier drug delivery systems, and then, more specifically, the significance and perspectives of peptide-based hydrogels. In particular, the interplay of intermolecular forces that govern the self-assembly of peptide hydrogels, progress made in understanding the distinct morphologies of hydrogels, and applications of non-canonical amino acids in hydrogel design will be discussed in more detail.

Aging affects structure and functions of all organs and systems in the organism. Significant changes in the hormonal levels are registered in elderly individuals. They often become a predisposition for chronic diseases, including cardiovascular, neurodegenerative, and metabolic disorders. Therefore, immense scientific efforts are concentrated in the investigation of molecular mechanisms and drugs with potential to diminish the senescent hormonal changes. Sirtuin 1 (SIRT1), a member of the sirtuin deacetylases family, has been extensively studied as regulator of multiple pathways related to antioxidant properties, optimal immune response and metabolism. SIRT1 plays a crucial role in regulating various hormonal pathways and maintaining homeostasis. In the present work we review the interplay between SIRT1 and hormonal regulations, including endocrine role of the hypothalamic-pituitary-thyroid, -adrenal, -gonadal, and -liver axes, of other endocrine glands and of non-endocrine tissues in aging body. The application of natural SIRT1 activators, such as resveratrol, curcumin, paeonol, and Buyang Huanwu Decoction, for treatment of senescence and aging is discussed. SIRT1 activators improve mitochondrial function, reduce oxidative stress, and promote longevity but their clinical application is limited by low bioavailability and poor permeability across biological barriers. For this reason, advanced delivery strategies, including nose-to-brain drug delivery and nanotechnology-based formulations, are reviewed.

Non-viral mediated plasmid DNA transfection by electroporation (EP) is an established method for gene transfection. In this study, the usefulness of direct EP at an intradermal (i.d.) site (D_EP) with implanted electrodes to achieve a high protein expression level was investigated. In addition, D_EP application with various intervals with a low application voltage was also evaluated to confirm its effect on protein expression. A higher protein expression level was observed after green fluorescent protein (GFP)- and luciferase-encoding DNA were delivered by i.d. injection followed by D_EP application. When luciferase expression was observed with an in vivo imaging system, continuous expression was confirmed over 21 days after i.d. injection followed by D_EP at 100 V. This approach provided increased gene expression levels compared with conventional EP methods via the stratum corneum layer. In addition, the effect of application voltage on luciferase expression was investigated; two-time applications (repeated D_EP) at 20 V with 5 min intervals showed similar luciferase expression level to single D_EP application with 100 V. Histological observations showed the skin became thicker after a single D_EP at 100 V, whereas no apparent thickness changes was confirmed after repeated D_EP at 20 V with 5 min intervals. This study revealed that direct i.d. voltage application achieved high protein expression levels even at low voltages. Skin is a promising administration site for DNA vaccines, so this approach may be effective in DNA vaccine delivery into skin tissue.

Today, polymeric Drug Delivery Systems (DDS) appear as an interesting solution against bacterial resistance, having great advantages such as low toxicity, biocompatibility, and biodegradability. In this work, two polyketones (PK) have been post-functionalized with taurinate (PKT) or sulfanilate (PKSK) and employed as biocompatible carriers for Vancomycin against bacterial infections. Mod-ified PKs were easily prepared by Paal-Knorr reaction and loaded with Vancomycin at variable pH. All polymers were characterized by FT-IR, DSC, TGA, SEM and elemental analysis. Antimicrobial activity was tested against Gram positive Staphylococcus aureus ATCC 25923 and correlated to the different pH used for its loading (between 2.3 and 8.8). Distinctively, minimum inhibitory con-centrations achieved with PKT and PKSK loaded with Vancomycin are similar, 0.23μg/mL and 0.24μg/mL respectively, i.e. six times lower that Vancomycin alone. The use of post-functionalized aliphatic polyketones has thus been demonstrated to be a promising way to obtain very efficient polymeric DDS.

Background/Objectives: Forceps delivery is a crucial obstetrical technique that has been increasingly underutilized in favor of cesarean delivery, despite numerous complications related to cesarean section. The major concerns in assisted vaginal birth (AVB) are the safety and long-term consequences. Thus, we aimed to investigate the neurodevelopmental outcome of children born with forceps delivery up to the age of seven. Methods: A prospective descriptive study was conducted from January 2011 to December 2016 among 49 women from our department in the Clinic for Gynecology and Obstetrics, University Clinical Center of Serbia. The study included women with term singleton cephalic pregnancies. Descriptive statistics were calculated for the baseline demographic and clinical features, whereas the logistic regression analysis was used to explore the association between various perinatal parameters and neurological status of newborns. The Sarnat and Sarnat classification was used to evaluate neurological status of newborns, while long-term neurodevelopmental outcome was assesed with Griffiths Mental Development Scale and additional questions based on the neurologist's clinical practice and experience. Results: Pathological neurological status of the newborn was found in 16.3%, with pathological ultrasound of CNS in 3%. A statistically significant association was observed with Apgar score, odds ratio of 0.575 (95% CI: 0.407–0.813, p = 0.002) and perinatal asphyxia, odds ratio of 9.882 (95% CI: 1.111–87.902, p = 0.04). However, this was unlikely to be related to the mode of delivery. Long-term adverse neurological outcome was seen in three cases, which accounts for 6.4%. These included mild disorders, such as delayed milestone, speech delay and motor clumsiness. Conclusion: The present study highlights the safety of forceps delivery regarding children's neurological outcomes at 7 years of age. This is an important contribution to the modern management of labor, especially in light of increasing rates of cesarean deliveries worldwide.

(1) Background: Although diagnostic criteria for massive hemorrhage with organ dysfunction such as disseminated intravascular coagulation associated with delivery have been empirically established based on clinical findings, strict logic has yet to be used to establish numerical criteria. (2) Methods: A dataset of 107 deliveries with ≥2,000 g of blood loss, among 13,368 deliveries from nine national perinatal centers in Japan between 2020 and 2023 was obtained. Twenty-three patients had fibrinogen levels <170 mg/dl, which is the initiation of coagulation system failure per our previous reports. Three of these patients had hematuria. We used six machine learning methods to identify the borderline criteria dividing the fibrinogen/fibrin/fibrinogen degradation product (FDP) planes, using 15 coagulation fibrinolytic factors. (3) Results: The boundaries of hematuria development on a two-dimensional plane of fibrinogen and FDP were obtained. If the FDP–fibrinogen/3–60 (mg/dl) value is positive, this indicates hematuria; otherwise, the case is non-hematuria, as demonstrated by the support vector machine method that seemed the most appropriate. (4) Conclusions: The borderline criterion dividing the fibrinogen/FDP plane for patients with hematuria that could be considered organ dysfunction in massive hemorrhage during delivery was obtained using artificial intelligence, and this method seemed to be useful.

Cancer, characterized by abnormal cell proliferation driven by genetic mutations, remains a significant health challenge. Tailoring effective therapies depends on factors like tumor location, grade, and stage, alongside patient condition. Leveraging Nano-carrier encapsulated drugs offers a promising avenue, as they accumulate preferentially at tumor sites, enhancing therapeutic efficacy while mitigating side effects. Polymeric Nano-carriers, with their customizable properties, further optimize drug delivery efficiency and specificity. Incorporating active targeting ligands such as antibodies, carbohydrates, peptides, folates, and aptamers-onto polymeric nanoparticle surfaces through techniques like functionalization, adsorption, and conjugation plays a pivotal role in directing therapeutic agents to tumor cells. Consequently, polymeric nanoparticles emerge as the carrier of choice for delivering drugs to various tumor types, including breast, colon, lung, prostate, liver, and spleen tumors.

Type 2 Diabetes Mellitus (T2DM) is one of the most common metabolic disorders, with a major involvement of oxidative stress in its onset and progression. Pioglitazone (Pio) is an antidiabetic drug which primarily works by reducing insulin resistance while Curcumin (Cur) is powerful antioxidant with o important hypoglycemic effect, also. The both drugs are associated with several drawbacks, such as reduced bioavailability, a short half-life time (Pio) as well as instability and poor water solubility (Cur), which limit their therapeutic use. In order to overcome these disadvantages, a new co-delivery (Pio, Cur) nanosystem based chitosan (CS) (CS-Pio-Cur NPs), was developed, and characterized in reference with simple nanosystems (CS-Pio NPs, CS-Cur NPs). The developed CS-based NPs (CS-Pio-Cur NPs, CS-Pio NPs, CS-Cur NPs) were physico-chemical characterized in terms of particle size (PS), entrapment efficiency (EF%) and loading capacity (LC%). The CS-Pio-Cur NPs proved increased or similar values of EE (88.95% ± 7.79 for Cur; 94.83% ± 9.89 for Pio) and LC% (24.25 % ± 1.62 for Cur; 3.5% ± 0.98 for Pio), in reference with simple nanosystems, CS-Cur NPs (EE = 82.46% ± 1.74; LC = 20.34% ± 0.94) and CS-Pio NPs) (EE = 96.31% ± 0.68; LC = 4.11% ± 0.47), respectively. The identification of APIs (Cur, Pio) loaded into CS matrix was performed using FR-IR spectroscopy and for simultaneously quantification of APIs (Cur, Pio) released from CS-Pio-Cur NPs, a HLPC method was developed and validated. Based on release study performed in different simulated fluids (SGF, SIF, SCF) it can be appreciated that developed CS-APIs NPs have favorable pharmacokinetic profile with good release in gastrointestinal tract.

Microcrystal delivery instruments are pivotal to perform serial femtosecond crystallography experiments at the XFEL facilities. We present a novel sample delivery technique based on a micro-tubing reeling system (MRS). Even though the tiny size of the micro-tubing, the MRS device has an advantage of operation without real-time position adjustment of the tube to match with the XFEL pulses. Moreover, the applicable repetition rate is more flexible than the previously reported chip-based one-dimensional fixed target system.

Glioblastoma (GB), even though not frequent, is an extremely aggressive brain tumor, with a strong impact on patient outcomes, in terms of both length and quality of life. The protocol estab-lished by Stupp and coworkers in 2005, based on radiotherapy and temozolomide chemotherapy, after maximum safe surgical resection, remains the gold standard for GB treatment. However, it is evident nowadays that the extreme GB intratumoral and intertumoral heterogeneity, invasive-ness and recurrence are not compatible with a routinary and unfortunately uneffective treatment. In this review article, we summarize the principal challenging issues in finding new valuable therapies for GB and focus on the impact that extracellular vesicle (EV) research and exploitation can have in the field. EVs are natural particles delimited by a lipidic bilayer and full of functional cellular content, released and uptaken by cells as key means of cell communications. Moreover, being stable in body fluids, well-immunotolerated, able to cross physiological, inter-species, and inter-kingdom barriers, and to target specific cells, releasing inherent or externally loaded functionally active molecules, EVs can be potentially ideal allies in fighting GB and assuring to GB patients a better prognosis. Here we report the main results obtained until now, focusing on both EV sources and molecular cargo used in the different functional studies, mainly in vivo. Finally, we perform a SWOT analysis reporting both the main advantages and the pitfalls of developing EV-based GB therapeutic strategies to highlight the main directions to explore for realizing the promise of EV exploitation for GB treatment.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

The study explores the potential of Cell-Penetrating Peptides (CPPs) for targeted drug delivery, particularly in anticancer applications. Despite certain drawbacks, such as short duration of action and poor stability in vivo, CPPs show promise when optimized through chemical modification or clever design. Advancements in targeted drug delivery using CPPs, especially for transporting anticancer drugs and imaging reagents, highlight their evolving efficacy. Four different CPP chains (7 alpha, 7 beta, 12 alpha, and 12 beta) and four in-house anticancer lead molecules were considered for the study. The CPPs were modeled and validated for in silico interaction analysis. Targeting proteins crucial in cell growth and signaling pathways, such as ADRM1, PSMD4, CDK1, CDK2, CDK4, CDK6, P53, and EGFR, presents a significant therapeutic opportunity. The in silico molecular interaction analysis involving CPP-conjugated lead molecules and these targets indicates favorable binding affinities, particularly with beta-confirmation 12 and 7 peptide chains. Notably, CPP conjugation enhances interactions without compromising ligand potentiality. This delicate balance emphasizes the role of CPPs in augmenting protein-ligand interactions, suggesting their potential benefits in targeted drug delivery, pending further optimization and experimental validation.

Hyaluronan has been considered in recent years as a potential naturally occurring modifiable scaffold that has the capability to absorb and release drugs over an extended period of time making it suitable as a chemotherapeutic delivery agent. Considering the limited treatment options available in the treatment of glioblastoma, in this review, we discuss the novel utilization of ultra high molecular weight hyaluronan - originally identified as a mechanism for maintaining longevity in the naked mole rat, as both a protective and extracellular matrix optimising scaffold, and a means to deliver therapy in resected brain tumors. The unique properties of this unique form of hyaluronan indicate potential future use in the prevention and treatment of both proliferative based and inflammation driven disease.

Recent advancements in nanotechnology have led to the development of multifunctional iron oxide nanoparticles, presenting new opportunities in cancer therapy. This study aimed to synthesize and evaluate citric acid-coated/ folic acid conjugated nanoparticles loaded with doxorubi-cin and investigate their efficacy in experimental tumor models. For synthesis, controlled co-precipitation method was employed to produce highly dispersive, multifunctional nanofluids with a narrow size distribution of iron oxide nanoparticles. Nanoparticles were characterized using Dynamic Light Scattering (DLS) and Electrophoretic Light Scattering (ELS) for size distribution and zeta potential, X-ray Diffraction (XRD) and Transmission Electron Microscopy (TEM) for structure and morphology, Vibrating Sample Magnetometry (VSM) for magnetic properties, and UV-Visible (UV-Vis) and Fourier-Transform Infra-red (FTIR) spectroscopy for modification confirmation. In vitro experiments employed RM1 (prostate cancer) and MEC1 (Chronic lymphocytic leukemia) cell lines to assess cytotoxicity and drug delivery efficiency. Fluorescence microscopy confirmed the intracellular delivery of doxorubicin by these nanoparticles, highlighting their potential for targeted therapy. As a result, nanoparticles conjugated with folic acid showed reduced efficacy over time. This study underscores the critical role of nanoparticle modifications in optimizing therapeutic outcomes. Future research should focus on further refining nanoparticle formulations and long-term effects in vivo, for development of effective and safe agents for targeted cancer treatment.

Activating the cytosolic innate immune sensor cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway via natural and synthetic agonists holds great potential for priming robust antitumor immunity. However, the effectiveness of STING agonists is often impeded by the insufficient tumor accumulation, poor cellular entry, and rapid clearance, thus leading to difficulty of their clinic translation. Herein, we apply the human serum albumin as the single-molecule nanoreactor to encapsulate SR-717 (SH-NPs) for enhanced targeting delivery efficiency and biological potency. SH-NPs with rational size distribution exhibited superior serum stability, considerable cellular uptake and abundant tumor accumulation, thus increasing the STING signaling including phosphorylation of STING-associated proteins (TBK1, IRF3), and cytokines secretion inside tumor region. Subsequently, SH-NPs remarkably reshape the immunosuppressive tumor microenvironment into an immunogenic one that boosts antitumor T-cell immunity and improves the therapeutic efficacy of checkpoint blockade against murine tumors. We also validate SH-NPs in freshly isolated human renal tumor tissues to highlight their clinic translation capability. These findings pave the way towards targeted STING agonist delivery for reinvigorated immunotherapy of intractable cancers.

Unmanned delivery technology using unmanned aerial vehicles (UAVs) has the potential to solve issues such as traffic congestion and labor shortages. We investigated a method to construct a route between the source and destination nodes in a wireless multi-hop network by installing a radio terminal in each house. If the relay functions of all nodes in the network are in operation, the number of control messages for route construction increases, and the message relay forwarding load of each node increases. Keeping all node pairs multi-hop connectivity, we establish a method to operate the relay function with as few nodes as possible. End nodes that have not activated the relay function connect to the relay node with the closest physical distance. In this paper, we propose methods for selecting nodes to operate the relay function. Specifically, one method is based on random selection, another method is based on the number of adjacent nodes, and a third method is based on the Multipoint Relay (MPR) of the Optimized Link State Routing Protocol (OLSR). For each method, we evaluate whether the route construction is available, the number of relay nodes, the total distance of constructed routes, and the distance in population-dense regions. We clarify the characteristics of each method, and the method based on MPR is the best for constructing a network suitable for UAV navigation routes. In addition, the smaller the number of relay nodes, the more unexpected collisions on the links due to route conflicts. We clarify the minimum node density required to apply the MPR method which reduces the number of relay nodes suppressing route conflicts.

Microneedle technology is a novel platform technology that revolutionizes ocular drug delivery and addresses critical challenges in the treatment of ocular diseases. Routine treatment methods, such as eye drops and intravitreal injections, suffer from low bioavailability and poor patient compliance. So, novel advanced platform technologies are required to overcome these challenges. Microneedle is a minimally invasive and promising alternative technique that helps precisely control drug delivery to targeted tissues and organs. This review investigates the potential impact of microneedle technology for eye care, underscoring recent advancements, underlying mechanisms, and emerging preclinical and clinical uses. Different types of microneedles, including solid, coated, dissolvable, and hollow, have demonstrated their potential and capability to bypass several barriers in the cornea and sclera. This ensures effective drug penetration and delivery. The current innovations in material science and fabrication methods have enhanced the safety and efficacy of microneedles, reducing discomfort and the chances of infections. These microneedle technologies offer sustained and controlled drug delivery, which could improve therapeutic outcomes for various disease conditions like age-related macular degeneration, glaucoma, diabetic neuropathy, etc. In the current review, recent preclinical and clinical studies emphasize microneedle-based ocular drug delivery's feasibility and potential benefits. These include improved pharmacokinetics, reduced dosing frequency, enhanced patient adherence, and, most importantly, microneedles offer versatile platforms for delivering a wide range of small and large molecules and gene therapies. Despite the exciting progress, obstacles such as regulatory barriers, scalability, and long-term biocompatibility persist. It will be essential to tackle these challenges through interdisciplinary research and partnerships to integrate microneedle technology into standard clinical use effectively. Ultimately, microneedle drug delivery offers a revolutionary method that has the potential to significantly enhance the treatment and results of ocular diseases, marking the dawn of a new era in eye care.

Numerous study reports on chitosan hydrogels in different forms such as films, porous structures, nanoparticles, and microspheres for biomedical applications, however, this study concentrates on their modifications with different crosslinking agents and observing their effects on drug loading and releasing capacities. Linear chitosan along with crosslinked by two major cross-linkers, i.e., genipin and disulfide have been used to formulate three different hydrogel systems. The cross-linking process is heavily impacted by the temperature and the pH conditions. Three different drugs, i.e., thymoquinone, gefitinib, and erlotinib are loaded in phosphate buffer solutions and infused with three different hydrogel systems, thus, a total of nine combinations are studied and analyzed for drug loading and releasing capabilities with Ultraviolet–visible (UV-Vis) spectroscopy. This study finds thymoquinone shows the lowest loading efficacy compared to two other drugs in all three systems. Gefitinib shows stable loading and releasing regardless of crosslinking systems and genipin crosslinked system shows stable loading and releasing with all three drug molecules. These experimental results agree well with the findings of our previously published results conducted with molecular dynamics simulations.

Background: Individuals living in rural areas often face challenges in accessing healthcare, increasing their risk of poor health outcomes. Farmers, a sub-population in rural areas, are particularly vulnerable to mental health issues and suicide, yet exhibit low rates of help-seeking behavior. The aim of our study was to develop an in-depth understanding of the issues influencing mental help-seeking among farmers living in rural areas from the perspectives of healthcare providers, as well as to explore the strategies providers use to navigate through these issues to effectively engage with this vulnerable population. Methods: We used a descriptive phenomenological approach to understand healthcare providers’ perspectives, experiences, and approaches to providing mental healthcare to farmer clients in rural areas. Semi-structured interviews were conducted with 21 participants between March and May 2023. Results: Our analysis yielded five thematic areas: (1) ensuring accessibility, (2) establishing relatability, (3) addressing stoicism and stigma, (4) navigating dual roles, and (5) understanding community trauma. Conclusions: Healthcare service delivery for farmers is multifaceted. This study fills a gap in knowledge by translating these the data to inform an evidence-based model and a list of recommendations for implementing agriculturally-informed practices in rural areas.

Heterodimeric approach has emerged as a promising method for simultaneously targeting multiple receptors on tumor cells using a single molecule. Simultaneous targeting of the prostate-specific membrane antigen (PSMA) and the gastrin-releasing peptide receptor (GRPr) holds the potential to improve the accuracy of prostate cancer diagnosis. This study aimed to develop and compare six alternative routes for stereoselective synthesis of heterobivalent conjugates designed to deliver the chelating agent DOTA to PSMA/GRPr receptors. The comparison of these alternative synthetic approach, considered such factors as efficiency, complexity, synthesis and purification characteristics, as well as yields of the target compounds has been made. Optimal conditions for the stereoselective synthesis of heterobivalent ligands to PSMA and GRP, which could serve as molecular platforms for the targeted delivery of therapeutic and/or diagnostic agents to these receptors, were determined. For synthesized heterobivalent ligand 26^x and heterobivalent conjugate with DOTA 27 complete signal assignment in ¹H, ¹³C, and ¹⁵N NMR spectra was achieved using 2D NMR techniques. Based on these data, comprehensive signal assignments were provided for all final compounds in their NMR spectra.

Post-operative chemotherapy is still required for the treatment of glioblastoma (GBM), and nanocarrier-based drug delivery has been identified as one of the most effective methods. However, the blood-brain barrier (BBB) and non-specific delivery to non-tumor tissues can significantly limit drug accumulation in tumor tissues and cause damage to nearby normal tissues. This study describes a targeted cancer therapy approach that uses AS1411 aptamer-conjugated nanospheres, 100-300 nm in size, loaded with doxorubicin (Dox) to selectively identify tumor cells overexpressing nucleolin (NCL) proteins. The study demonstrates that the active target model, which employs aptamer-mediated drug delivery, is more effective than nonspecific enhanced permeability and maintenance (EPR)-mediated delivery and passive drug delivery in improving drug penetration and maintenance in tumor cells. Additionally, the study shows the potential for anticancer effects through 3D spheroidal and in vivo GBM xenograft models. The DNA-protein hybrid nanospheres utilized in this study offer numerous benefits, such as efficient synthesis, structural stability, high drug loading, dye labelling, biocompatibility, and biodegradability. When combined with nanospheres, the 1411 aptamer has been shown to be an effective drug delivery carrier for precisely targeting tumors. This combination has the potential to produce anti-tumor effects in active targeted therapy of GBM.

Curcumin, a polyphenol with a rich history spanning two centuries, has emerged as a promising therapeutic agent targeting multiple signaling pathways and exhibiting cellular-level activities that contribute to its diverse health benefits. Extensive preclinical and clinical studies have demonstrated its ability to enhance the therapeutic potential of various bioactive compounds. While its reported therapeutic advantages are manifold, predominantly attributed to its antioxidant and anti-inflammatory properties, its efficacy is hindered by poor bioavailability stemming from inadequate absorption, rapid metabolism, and elimination. To address this challenge, nano-delivery systems have emerged as a promising approach, offering enhanced solubility, biocompatibility, and therapeutic effects for curcumin. We have analyzed the knowledge on curcumin nano-encapsulation and its synergistic effects with other compounds, extracted from electronic databases. We discuss the pharmacokinetic profile of curcumin, current advancements in nano-encapsulation techniques, and the combined effects of curcumin with other agents across various disorders. By unifying existing knowledge, this analysis intends to provide insights into the potential of nano-encapsulation technologies to overcome constraints associated with curcumin treatments, emphasizing the importance of combinatorial approaches in improving therapeutic efficacy. Finally, this compilation of study data aims to inform and inspire future research into encapsulating drugs with poor pharmacokinetic characteristics and investigating innovative drug combinations to improve bioavailability and therapeutic outcomes.

The last 20 years have seen significant advancements in polymeric drug delivery methods. A formulation or a system that makes it possible for a medicinal ingredient to be injected into the body is known as polymeric drug delivery1. The key choice for many novel medication delivery methods is made achievable by biodegradable and bio-reducible polymers. The research's prospects for practical applications have necessitated the field's development—the choice for a lot of new drug delivery systems. The prospects of the research for practical applications are required for the development in the field. Polymeric drug delivery methods have been developed from natural polymers like arginine, chitosan2, dextrin, polysaccharides, poly (glycolic acid), poly (lactic acid), and hyaluronic acid. Regarding polymeric drug delivery1, synthetic polymers such as poly(2-hydroxyethyl methacrylate), poly(N-isopropyl acrylamide), poly(ethylenimine), dendritic polymers, biodegradable, and bioabsorbable polymers have all been considered. Polymeric drug delivery has also been addressed by focusing on drug-free macromolecular therapies, biomimetic and bio-related polymeric systems, and targeting polymeric drug delivery. Pharmaceutical fields are seeing a tremendous rise in the development of polymeric drug delivery methods based on natural and manmade polymers. The successful advancements in the utilization of biocompatible and bio-related copolymers and dendrimers in cancer treatment, including their application as vehicle systems for highly effective anticancer medications3. A new paradigm for the development of polymeric drug and gene delivery systems will be possible through the fusion of viewpoints from the synthetic and biological domains.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

(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.

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.

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.