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.

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.

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.

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.

Polyelectrolyte multilayers (PEMs) deposited on porous composite polylactic acid/poly(ε-caprolactone) substrates were studied. The substrates were previously charged in a corona discharge. Time dependences of the normalized surface potential for positively and negatively charged electrets were investigated. The morphology of the obtained porous substrates was examined by means of scanning electron microscopy (SEM). The chitosan and the casein polyelectrolytes were deposited on the substrates using the layer-by-layer (LbL) technique. A drug loading efficiency and the release kinetics were determined spectrophotometrically.

Transdermal drug delivery systems have become an intriguing research topic in healthcare technology and one of the most frequently developed pharmaceutical products in the global market. In recent years, researchers and pharmaceutical companies have made significant progress in developing new solutions in the field. This study sheds light on current trends, collaboration patterns, research hotspots, and emerging frontiers of transdermal drug delivery. Herein, a bib-liometric and patent analysis of data recovered from Scopus and The Lens databases, respectively, is reported over the last 20 years. From 2000 to 2022, the annual global publications increased from 131 in 2000 to 659 in 2022. Researchers in the United States, China, and India produced the highest number of publications. Likewise, most patent applications have been filed in the USA, China, and Europe. The recovered patents are 7,275, grouped into 2,997 patent families, of which 314 were granted. This study could support the work of decision-makers, scientific managers, or scientists to create new business opportunities or save money, time, and intellectual capital, thus, defining when a research or technology project should be a priority or not.

Microfluidic technology has become a powerful tool for several applications in chemistry, physics, biology, and engineering. Benefiting from the advantages of flowing fluids in the laminar regime, droplet-based microfluidics enable the development of various delivery systems based on food-grade emulsions, such as multiple emulsions, microgels, microcapsules, solid lipid micro-particles, and giant liposomes. Besides, by manipulating fluids on a micrometer scale with low-energy demand, it is possible to control the size, shape, and dispersity of droplets generated, which makes microfluidic emulsification an excellent strategy to modulate delivery system properties depending on the entrapped compound type. Thus, this review points out the most current advances in droplet-based microfluidic processes, in which food-grade materials were successfully utilized to develop simple and complex delivery systems. In that context, we sum-marized the principles of droplet-based microfluidics, introducing the most common microde-vices geometries, manufacturing materials, and forces involved in the different droplet generation processes within the microchannels. Subsequently, the encapsulated compound type, classified as lipophilic or hydrophilic functional compounds, was used as a starting point to present current advances in delivery systems based on food-grade emulsions and assembly using microfluidic technologies. Finally, we discuss the limitations and perspectives of scale-up in droplet-based microfluidic approaches, including the challenges that have limited the transition of microfluidic processes from lab-scale to industrial-scale.

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.

Interpolyelectrolyte complexes Eudragit® EPO/L100 received in different pH were characterized by different degree of swelling in mimicking fasted stomach medium (0.1 M HCl) and saved their shape during 6 hours of the experiment. The microenvironmental changes in IPECs structure during swelling testing were inves-tigated using FT-IR spectroscopy, thermal and elemental analysis. Both samples of IPECs during swelling were transformed to a similar structure with approximately the same composition. IPEC samples showed bioadhesive properties that was not significantly different from the positive control (Carbopol) in the test with the mucin compacts. The release rate of metronidazole (class I BCS) from IPEC matrices increased with the increasing degree of swelling. IPEC 1 provided 49.62 ± 6.20% and IPEC 2 – 87.69 ± 5.15 % of metronidazole release after 6 hours in mimicking fasted stomach medium (0.1 M HCl). Total amount of released acyclovir (class III BCS) from IPEC 1 was 25.76 ± 5.67 % and from IPEC 2 was 21.48 ± 5.00 %. Release of both drugs was controlled by relaxation of polymeric chains in matrices according to the Peppas-Sahlin model. According to the received results, investigated interpolymer complexes are perspective for further evalua-tion as carriers for gastroretentive bioadhesive systems.

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.

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.

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.

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.

The release profiles of methotrexate, an anticancer drug, from the monoolein liquid crystalline cubic phases were studied. The cubic phases were used either in the form of a lipidic film deposited onto a glassy carbon electrode surface or in the dispersed form of magnetocubosomes, which are considered a prospective hybrid drug delivery system. Commonly, cubosomes or liposomes are employed, but not in the case of toxic methotrexate, known to block receptors responsible for folate transport into the cells. The release profiles of the drug from the lipidic films were monitored electrochemically and described using the Higuchi model. They were also modified via changes in temperature; the release was faster, although deviating from the model when the temperature was increased. Magnetocubosomes - cubic phase nanoparticles containing hydrophobic magnetic nanoparticles placed in an alternating magnetic field of low frequency and amplitude, stimulated drug release from the suspension, which was monitored spectroscopically. These new biocompatible hybrid materials are very promising, allowing to control the release of the drug at the appropriate sites, but do require further investigations into their in vitro cytotoxicity and in vivo biodistribution.

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.

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.

Lung cancer (LC) is one of the leading causes of cancer occurrence and mortality worldwide. Treatment of patients with advanced and metastatic LC presents a significant challenge as malignant cells use different mechanisms to resist chemotherapy. Drug resistance (DR) is a complex process that occurs due to a variety of genetic and acquired factors. Identifying the mechanisms underlying DR in LC patients and possible therapeutic alternatives for more efficient therapy is a central goal of LC research. Advances in nanotechnology resulted in the development of targeted and multifunctional nanoscale drug constructs. The possible modulation of the components of nanomedicine, their surface functionalization, and encapsulation of various active therapeutics provide promising tools to bypass crucial biological barriers. These attributes enhance the delivery of multiple therapeutic agents directly to the tumor microenvironment (TME), resulting in reversal of LC resistance to anticancer treatment. This review provides a broad framework for understanding the different molecular mechanisms of DR in lung cancer; presents novel nanomedicine therapeutics aimed to improve the efficacy of treatment of various forms of resistant LC; outlines current challenges in using nanotechnology for reversing DR; and discusses the future directions for clinical application of nanomedicine in management of LC resistance.

Transdermal drug delivery systems (TDDS) are designed to administer a consistent and effective dose of medication through the patient's skin. These pharmaceutical preparations are self-contained, discrete dosage forms designed to be placed topically on intact skin to release the active component at a controlled rate by penetrating the skin barriers. This medication provides a continuous and prolonged administration of a substance at a consistent rate. TDDS, or transdermal drug delivery system, has gained significant attention as a non-invasive method of administering drugs to vulnerable patient populations, such as pediatric and geriatric patients. This approach is considered easy to administer and helps overcome bioavailability issues associated with conventional drug delivery, which can be hindered by poor absorption and metabolism. TDDS has various advantages compared to conventional methods of drug administration. It is less intrusive, more patient-friendly, and can circumvent first-pass metabolism and the corrosive acidic environment of the stomach that happens when medications are taken orally. Multiple methodologies have been devised to augment the transdermal permeability of diverse pharmaceutical substances. Recent advancements in transdermal drug delivery systems have facilitated the precise delivery of medications to the intended site of action by improving the penetration of drugs through the outermost layer of the skin, known as the stratum corneum, resulting in enhanced drug availability throughout the body. This review seeks to provide a concise overview of the several methods employed in the production of TDDS, as well as their evaluation, therapeutic uses, clinical considerations, and current advancements. These advancements have resulted in the development of intelligent, biodegradable, and highly efficient transdermal drug delivery systems.

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.

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.

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.

Traditional methods for discovery and development of new drugs can be a very time-consuming and expensive process because it includes several stages such as compound identification, pre-clinical and clinical trials before the drug is approved by the US Food and Drug Administration (FDA). Therefore, drug repurposing, namely using currently FDA-approved drugs as therapeutics for other diseases than what they are originally prescribed for, is emerging to be a faster and more cost-effective alternative to current drug discovery methods. In this paper, we have described a three-step in silico protocol for analyzing transcriptomics data using online databases and bioinformatics tools for identifying potentially repurposable drugs. The efficacy of this protocol was evaluated by comparing its predictions with the findings of two case studies of recently reported repurposed drugs: HIV treating drug Zidovudine for the treatment of Dry Age-Related Macular Degeneration and the antidepressant Imipramine for Small-Cell Lung Carcinoma. The proposed protocol successfully identified the published findings, thus demonstrating the efficacy of this method. In addition, it also yielded several novel predictions that have not yet been published, including the finding that Imipramine could potentially treat Severe Acute Respiratory Syndrome (SARS), a disease that currently does not have any treatment or vaccine. Since this in-silico protocol is simple to use and does not require advanced computer skills, we believe any motivated participant with access to these databases and tools would be able to apply it to large datasets to identify other potentially repurposable drugs in the future.

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.

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.

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.

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.

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.

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.

Nano-drugs and nano-delivery systems are rapidly evolving, with new strategies emerging in the current practices. The evolution of these technologies began with modifying the chemical structure, progressing to supramolecular ionic complexes, and culminating in elegant ad hoc delivery systems. Nanoparticles have numerous benefits as a carrier system for delivering therapeutic agents to intra-arterial sites. These benefits include their subcellular size, targeted surfaces, good suspensibility, and uniform dispersity, making them an ideal choice for catheter-based delivery. Despite the advancements made in the field of nano-drugs and nano-delivery systems, there are still some hurdles to overcome in terms of their commercial availability.The current review presents an updated summary of recent advancements in nano-drugs and nano-delivery systems, including their commercial availability. We aim to discuss the present challenges and prospects of commercially available nano-drugs and nano-delivery systems. Here, we provide a precise and informative overview of the current state of these technologies and underscore the potential they hold for future developments. Further, we have categorized commercially available modifications, name, parent company and their main applications in nano-drugs.

This report provides a comprehensive overview of occupational asthma and respiratory hypersensitivity, focusing on some chemicals used in the workplace Includes numerous case studies and research papers related to occupational exposure methacrylates, such as HEMA-HPMA, and respiratory hypersensitivity are discussed And the relationship is explored The book also examines asthma pathophysiology, emerging drug delivery systems used to treat asthma, and the potential of nanoparticles , dendrimers and micellar systems have to improve pulmonary drug delivery in detail The worldwide prevalence of asthma is highlighted, with higher rates in high-GDP countries. The book highlights the need to improve asthma diagnosis, treatment and biomarkers, particularly in rural and low-income countries where the disease is often underdiagnosed and inadequately treated, and discusses the role of inflammation in asthma, in particular secondary inflammation characterized by specific cytokines and inflammation cells In addition, the paper explores various drug delivery methods, such as parenteral and parenteral drugs, pressurized inhalers (pMDIs), dry powder inhalers ( DPIs), nebulizers, nanoparticles, liposomes, micellar systems, microparticles , dendrimers, and gene therapy . These systems aim to increase pulmonary delivery of drugs and improve clinical outcomes. The potential of dendrimer bilirubin-based nanoparticles and micellar systems in the treatment of asthma and lung inflammatory diseases, including asthma, has been discussed in summary, this paper provides an overview of occupational asthma and respiratory hypersensitivity, and this discussion highlights the association between methacrylate exposure and respiratory hypersensitivity.

The similarities between exosomes and liposomes, together with the high organotropism of several types of exosomes, have recently prompted the development of engineered-exosomes or exosome-mimetics, which may be artificial (liposomal) or cell-derived vesicles, as advanced platforms for targeted drug delivery. Here we provide the current state-of-the-art of using exosome or exosome-inspired systems for drug delivery. We review the various approaches investigated and the shortcomings of each approach. Finally the challenges identified up-to-date in this field are summarized.

Antibody-mediated targeting is an efficient strategy to enhance the specificity and selectivity of polymer nanomedicines towards the target site, typically a tumor. However, direct covalent coupling of an antibody with a polymer usually results in a partial damage of the antibody binding site accompanied with a compromised biological activity. Here, an original solution based on well-defined non-covalent interactions between tris-nitrilotriacetic acid (trisNTA) and hexahistidine (His-tag) groups, purposefully introduced to the structure of each macromolecule, is described. Specifically, trisNTA groups were attached along the chains of a hydrophilic statistical copolymer based on N-(2-hydroxypropyl)methacrylamide (HPMA), and at the end or along the chains of thermo-responsive di-block copolymers based on N-isopropylmethacrylamide (NIPMAM) and HPMA; His-tag was incorporated to the structure of a recombinant single chain fragment of an anti-GD2 monoclonal antibody (scFv-GD2). Static and dynamic light scattering analyses confirmed that mixing of polymer with scFv-GD2 led to the formation of polymer/scFv-GD2 complexes; those prepared from thermo-responsive polymers formed stable micelles at 37 °C. Flow cytometry and fluorescence microscopy clearly demonstrated antigen-specific binding of the prepared complexes to GD2 positive murine T-cell lymphoma cells EL-4 and human neuroblastoma cells UKF-NB3, while no interaction with GD2 negative murine fibroblast cells NIH-3T3 was observed. These non-covalent polymer protein complexes represent a new generation of highly specific actively targeted polymer therapeutics or diagnostics.

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.

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.

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.

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.

Chitosan is a cationic polysaccharide usually obtained by alkaline deacetylation of chitin poly(N-acetylglucosamine). It is biocompatible, biodegradable, mucoadhesive and non-toxic. These excellent biological properties make chitosan a good candidate for a platform in developing drug delivery systems having improved biodistribution, increased specificity and sensitivity, and reduced pharmacological toxicity. In particular, chitosan nanoparticles are found to be appropriate for non-invasive routes of drug administration: oral, nasal, pulmonary and ocular routes. These applications are facilitated by the absorption-enhancing effect of chitosan. Many procedures for obtaining chitosan nanoparticles have been proposed. Particularly, the introduction of hydrophobic moieties into chitosan molecules by grafting to generate a hydrophobic-hydrophilic balance promoting self-assembly is a current and appealing approach. The grafting agent can be a hydrophobic moiety forming micelles that can entrap lipophilic drugs or it can be the drug itself. Another suitable way to generate self-assembled chitosan nanoparticles is through the formation of polyelectrolyte complexes with polyanions. This paper reviews the main approaches for preparing chitosan nanoparticles by self-assembly through both procedures and illustrates the state of the art of their application in drug delivery.

Nanoparticles have been used as a novel drug delivery system. Drug-incorporated nanoparticles for local delivery might optimize the efficacy and minimize the side effects of drugs. The efficacy and safety of intratracheal administration of prostacyclin analog (beraprost)-incorporated nanoparticles and imatinib, a PDGF-receptor tyrosine kinase inhibitor, -incorporated nanoparticles in Sugen-hypoxia-normoxia or monocrotaline rat models of PAH and in human PAH-pulmonary arterial smooth muscle cells have been reported. The use of inhaled drug-incorporated nanoparticles might be a novel approach for treatment of PAH.

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.

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.

The active form of fingolimod (FTY720; FT) is a sphingosine-1-phosphate receptor agonist with potential ocular applications. The goal of the present study was to develop an FT-loaded nanoemulsion (NE; FT-NE) formulation for the efficient and prolonged delivery of FT to the posterior segment of the eye through the topical route. FT-NE formulations were prepared with homogenization followed by probe sonication method. The lead FT-NE formulation (0.15% and 0.3% w/v loading), comprising soybean oil as lipid and Tween® 80 and Poloxamer 188 as surfactants, was further evaluated for in vitro release, surface morphology, filtration sterilization, and stability at refrigerated temperature. The formulation, at both dose levels, showed desirable physicochemical characteristics, a nearly spherical shape with homogenous nanometric size distribution, and was stable for 180 days (last time point checked) at refrigerated temperature post-filtration through polyethersulfone (0.22 µm) membrane. In vitro release studies showed prolonged release, compared with the control FT solution (FT-S), over 24 h. The results from these studies demonstrate that the FT-NE formulation can serve as a viable platform for the ocular delivery of FT through the topical route.

The reproductive health of women is governed by an optimal balance between the host-microbiota interaction. Depletion in the beneficial vaginal microflora caused by depletion of Lactobacillus species and increased proliferation of pathogens results in gynecological infections. Among women of reproductive age, vaginal infections are increasingly prevalent. Attaining therapeutic efficacy using conventional formulations remains a challenge as vaginal fluids quickly remove or dilute the therapeutic formulations. Hydrogels have been widely exploited for targeted delivery of therapeutics directly into the vaginal mucus. With careful choice of polymers (natural, synthetic or semi-synthetic) hydrogels with specific properties such as stimuli-responsiveness, antimicrobial, and muco-adhesiveness can be tailored for higher therapeutic efficacy. In this review, the advnances in hydrogel strategies for the treatment of vaginal infections is presented with emphasis on the types and properties that play a significant role in vaginal drug delivery systems.

Over the few decades, cancer-associated mortalities and morbidities were continuously increased worldwide despite sophisticated technological advancements. Pharmaceutical interventions associated with drugs exhibit a high degree of side effects and toxicities in addition to very high costs. Subsequently, to reduce or to vanish the side effects and high costs, researchers are now exploring natural bioactive compounds such as quercetin in its nanoformulations along with biologics as cargo delivery vehicles. Quercetin along with mesenchymal stromal lineage-derived extracellular vesicles (EVs) possesses an anti-cancer potential that can be explored to treat hepatocellular carcinoma (HCC). Exerting enhanced effect, nano quercetin synergistically with EVs triggers the anti-cancer mechanisms by regulating and dysregulating several signalling mechanisms including NF-κB, p53, JAK/STAT, MAPK, Wnt/β-catenin and PI3K/AKT, in addition to PBX3/ERK1/2/CDK2, and miRNAs modulation. In addition, findings regarding the potential checkpoints of anti-cancer signalling pathways were investigated that offer opportunities to develop engineered EVs incorporated with nano quercetin for the development of novel therapeutics to treat HCC in future. In this present mechanistic review, we abridged the regulation of such signalling mechanisms synergetic approach of nano quercetin and EVs. The regulatory role of EVs in the manifestation of innumerable miRNAs has also been tailed with special context to HCC.

The number of people affected by eye conditions is growing every year, due to the popularity of electronic devices and an aging population. In the world of medicine, accomplishing eye medication administration has always been a difficult task. Despite the fact that there are many eye drops on the market, most of them have important limitations due to quick clearance mechanisms and ocular barriers. One solution with tremendous potential is the contact lens used as medication delivery vehicle to bypass this constraint. Therapeutic contact lenses for ocular medication delivery have attracted a lot of attention because they have the potential to improve ocular bioavailability, patient compliance, and reduce side effects. However, it is essential not to compromise essential features such as water content, optical transparency, and modulus in order to target successful in vitro and in vivo sustained drug delivery profile from impregnated contact lenses. Aside from difficulties like drug stability and burst release, the changing of lens physical and chemical properties caused by therapeutic or non-therapeutic components can limit the commercialization potential of pharmaceutical-loaded lenses. Research has progressed towards bioinspired techniques and smart materials to improve the efficacy of drug-eluting contact lenses. The bioinspired method uses bioinspired polymeric materials to improve biocompatibility, a specialized molecule recognition technique called molecular imprinting, or a stimuli-responsive system to improve biocompatibility and support drug delivery efficacy of drug-eluting contact lenses. This review encompasses strategies of material design, lens manufacturing and drug impregnation under the current auspices in ophthalmic therapies and projects an outlook onto future opportunities in the field of eye conditions management by means of active principles-eluting contact lens.

Hydrogels prepared from natural polymer have attracted extensive attentions in biomedical fields such as drug delivery, wound healing, and regenerative medicine due to their good biocompatibility, degradability and flexibility. This review outlines the commonly used natural polymer in hydrogel preparation, including cellulose, chitosan, collagen/gelatin, alginate, hyaluronic acid and starch. The polymeric structure and process/synthesis of natural polymers are illustrated, and natural polymer-based hydrogels including the hydrogel formation and properties are elaborated. Subsequently, the biomedical application of hydrogels based on natural polymer in drug delivery, tissue regeneration, wound healing and other biomedical field is summarized. Finally, the future perspectives of natural polymers and hydrogels based on them are discussed. For natural polymer, novel technologies such as enzymatic and biological methods are developed to improve the structural properties and the development of new natural based polymers or natural polymer derivatives with high performance is still very important and challenging. For natural polymer-based hydrogels, novel hydrogel materials, like double-network hydrogel, multifunctional composite hydrogels and hydrogel microrobots are designed to meet the advanced requirements in biomedical application, and new strategies such as dual-crosslinking, microfluidic chip, micropatterning and 3D/4D bioprinting, have been explored to fabricate advanced hydrogel materials with designed properties for biomedical application. Overall, natural polymeric hydrogels have attracted increasing interests in biomedical application, and the development of novel natural polymer-based materials and new strategies/methods for hydrogel fabrication is badly desirable and still challenging.

In this work, alkylammonium-functionalized hollow mesoporous silica as nonocarrier of drugs was synthesized to realize enhanced cancer therapy by pH stimuli for sustained drug release. First, functionalized hollow mesoporous silica nanoparticles (Hollow MSNs) were synthesized using dodecyl dimethyl(3-sulfopropyl)ammonium hydroxide (DDAPS), sodium dodecyl sulfate (SDS), and triethanolamine as structure-directing agents, and tetraethyl orthosilicate (TEOS) and N-trimethoxysilypropyl-N,N,N-trimethylammonium chloride (TMAPS) as silica sources under basic condition via the sol-gel process. The structure and morphology of the alkylammonium-functionalized hollow mesoporous silica nanoparticles (Hollow MSN-N+CH3) were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), N2 adsorption-desorption analysis, and Fourier-transform infrared (FT-IR) spectroscopy. The functionalized hollow MSNs had a particle size of about 450 nm and a shell thickness of about 60 nm with uniform size. The nanoparticle had a surface area of 408 m2g-1, pore volume of 0.8 cm3g-1 and a uniform pore diameter of 45.9 Å. In the cancer cell viability test with MCF-7 cell, fludarabine-incorporated and alkylammonium-functionalized hollow mesoporous silica nanoparticles (Flu/Hollow MSN-N+CH3) showed excellent cancer cell death comparable with pure fludarabine drug with the controlled drug release by pH stimuli. It is considered that our current materials have the potential applicability as pH-responsive nanocarriers in the field of cancer therapy.

Polymeric microparticles of polyethyleneglycol-polylactic acid-co-glycolic acid (PEG-PLGA) are widely used as drug carriers for a variety of applications due to their unique characteristics. Herein, we developed a novel method for the synthesis of uniformly sized microparticles via coaxial flow-phase separation. The study evaluated the effect of various process parameters on microparticle size and polydispersity including polymer concentration, stirring rate, surfactant concentration, and the organic/aqueous phase flow rate and volume ratio. The results demonstrated that stirring rate and polymer concentration had the most significant impact on the mean particle size and distribution whereas surfactant concentration had the most substantial impact on the morphology of particles. Several microparticle formulations yielding particle sizes in the range of (5-50 µm), morphology, and concentration were synthesized as a demonstration of the tunability and scalability of this method. Notably, by controlling the process parameters microparticles of less than ~ 7 μm could be made using polymer concentrations varying by an order of magnitude. Finally, we demonstrated the tunability and scalability of this method by showing a 10-fold increase in encapsulation efficiency, a 3-fold increase in drug loading of a model hydrophilic drug, and modified release kinetics in microparticle formulations of comparable sizes but different polymer concentrations.

Polymeric hydrogels are promising polymeric functional materials that have been widely used in the biomedical field as an emerging carrier of various therapeutic agents. Polymeric hydrogels as a carrier of therapeutics can leverage therapeutically beneficial outcomes of drug delivery than systemic chemotherapy and can provide spatial and temporal control over the release of various therapeutic agents. Polymeric hydrogels are cross-linked three-dimensional networks constructed by hydrophilic polymers and they are capable of absorbing and re-taining a large amount of water. Polymeric hydrogels share many physiochemical features with natural tissues due to their water abundance, biomimetic microstructure, and intrinsic flexibility. Polymeric hydrogels have excellent biocompatibility, biodegradability, and lower toxicity. Polymeric hydrogels enhance the convenience and efficiency of drug delivery by assisting in situ gelation and controlling drug release by changing their volume and other properties when it encounters some stimuli (e.g., heat, pH, light, and ultrasound). This review aims to outline the overview of polymeric hydrogels, properties, types, advantage, disadvantages, characteri-zation, and their application with present status and future perspective used for the delivery of therapeutics in pharmaceutical and biomedical sciences.

The supramolecular based macrocyclic amphiphiles have attracted great attention in the field of drug delivery due to their unique self-assembling nature. Therefore, these macrocycles are used as nanocarriers for the delivery of poor water soluble drugs, and also for those which have lower permeability, and cannot cross the barrier to reach the desired site. Herein, we design and synthesized a new supramolecular amphiphilic macrocycle to overcome these problems. The macrocycle was synthesized in two steps. In first step 4-hydroxybenzaldehyde was treated with 1-bromotetradecane to obtain a derivatized product which was then treated with resorcinol to cyclize and get calix(4)resorcinarene based supramolecular amphiphilic macrocycle. The synthesized macrocycle and intermediate products were characterized by Mass spectrometry, IR and 1H-NMR spectroscopic techniques. The amphiphile was screened for biocompatibility studies, vesicles formation, and then Amphotericin-B was loaded in the supramolecular amphiphile based vesicles and was characterized for shape, size, homogeneity, surface charge, drug entrapment, in-vitro release profile and stability through atomic force microscopy (AFM), Zetasizer, HPLC and FT-IR. Amp-B loaded macrocycle based vesicles were investigated for in-vivo bioavailability in rabbits. The synthesized macrocycle was nontoxic in cancer cells, hemo-compatible and safe in mice. The drug-loaded macrocycle based vesicles appeared spherical, nano-ranged, and homogeneous in size with negative surface charge and were able to load an increased amount of drug. The vesicles are stable upon storage and when incubated with gastric simulated fluid. Amp-B increased oral bioavailability was achieved when delivered in synthesized macrocycle based vesicles. These results point out that the synthesized supramolecular amphiphile is an efficient nanocarrier to enhance the oral bioavailability of lipophilic drugs

Nanomaterials such as pH-responsive polymers are promising for targeted drug delivery systems, due to the difference in pH between tumor and healthy regions. However, there is a significant concern about the application of these materials in this field due to their low mechanical resistance, which can be mitigated by combining these polymers with mechanically resistant inorganic materials such as mesoporous silica nanoparticles (MSN) and hydroxyapatite (HA). Mesoporous silica has interesting properties such as high surface area and hydroxyapatite has been widely studied to aid in bone regeneration, providing special properties adding multifunctionality to the system. Furthermore, fields of medicine involving luminescent elements such as rare earth are an interesting option in cancer treatment. The present work aims to obtain a pH-sensitive hybrid system based on silica and hydroxyapatite with photoluminescent and magnetic properties. The nanocomposites were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), nitrogen adsorption methods, CHN elemental analysis, Zeta Potential, scanning electron microscopy (SEM), and transmission electron microscopy (TEM), vibrational sample magnetometry (VSM), and photoluminescence analysis. Incorporation and release studies of the antitumor drug doxorubicin were performed to evaluate the potential use of these systems in targeted drug delivery. The results showed the luminescent and magnetic properties of the materials and showed suitable characteristics for application in the release of pH-sensitive drugs.

Rottlerin(R) is a natural extract from Mallotus philippensis with antiviral properties. Feline Infectious Peritonitis (FIP) is a fatal disease characterized by systemic granulomatous inflammation and high mortality, with no established prevention or cure. We investigated antiviral effect of liposome loaded R, Rottlerin-liposome(RL) against Feline infectious peritonitis virus (FIPV), the causative agent. We demonstrated that R and RL inhibited FIPV replication in dose dependently with a PKCδ related manner, not only in the early endocytosis step but also in the late step of replication. RL resolved the low solubility issue of rottlerin and improved its inhibition efficacy at the cellular level. Based on these findings, we suggest that RL has a value for further research as a potential antiviral agent against FIPV.

Hydrogel microneedles are a promising technology for the delivery of different types of medicines locally and painlessly, as well as ISF extraction. As the hydrogel microneedles are inserted into the tissue, they swell and release drugs. To improve the effectiveness of this technology in delivering medicine at controlled and desirable doses and intervals, a deep understanding of the mechanism of drug delivery inside the microneedles is required. In this work, drug diffusion inside a tapered microneedle is investigated using numerical simulation. The microneedle is divided into many small elements, and the mass transfer equation of meloxicam is solved in each element over time. The skin is simulated as the sink in the microneedle surface for drug absorption. Simulations are performed for different sizes of microneedles. For a microneedle with a height of 500 µm and a base diameter of 250 µm, the drug completely penetrates the skin within 3.2 seconds. The rate of drug diffusion from the tip of the microneedle is higher than diffusion from the side area near the microneedle base. The obtained data demonstrate that in addition to the height and the base diameter, the microneedle’s aspect ratio, h/d, also affects the time of drug diffusion. We present a nonlinear equation to predict the time of complete drug diffusion as a function of the microneedle geometrical parameter, including the height and base diameter. The proposed equation calculates the total drug diffusion time with an error of less than 7% for all studied cases. Predicting drug diffusion patterns inside microneedles can be helpful in the biomedical field, especially in the drug-controlled release system for the optimization of drug delivery.

Nanomedicine holds great potential to devise better drug delivery systems (DDSs). However, many reported nanomedicines still fall short of commercial requirements including specific targetability, scale-up manufacturing and safety. Cell/tissue based carriers, including cell membrane vehicle and exosome, are biocompatible and targeting platforms but usually suffered from low yields and unstable reproducibility. Here in this study, we proposed the concept and preparation of reconstituted lipid nanoparticles (rLNPs) to develop highly reproducible cell/tissue based lipid nanoparticles (LNPs) for drug delivery, which holds the potential as a versatile drug delivery platform. The whole lipids of cell or tissue were firstly extracted and then prepared into rLNPs using solvent diffusion method. In this way, the preparation of ultra-small (~20 nm) rLNPs can be easily applied to both cell (mouse breast cancer cell line, 4T1) and tissue (mouse liver tissue). Our results demonstrated that mouse liver tissue derived rLNPs can be further labeled/modified with imaging, targeting or other functional moieties. Furthermore, rLNPs were highly biocompatible and capable of loading different drugs including doxorubicin hydrochloride (Dox) and curcumin (Cur). Most importantly, Dox loaded rLNPs (rLNPs/Dox) showed preferable in vitro and in vivo anticancer performance. Therefore, rLNPs might be a versatile drug delivery platform for future application in the treatment of a variety of diseases.

There are various biomaterials in nature, but none fulfills all the requirements. Cellulose, eco-friendly material-based biopolymers, have been advanced biomedicine to satisfy most market demand and circumvent many ecological concerns. This review aims to present an overview of the state of the art in cellulose's knowledge and technical biomedical applications. It included an extensive bibliography of recent research findings for fundamental and applied investigations. The chemical structure of cellulose allows modifications and simple conjugation with several materials, including nanoparticles, without tedious efforts. Cellulose-based materials were used for biomedicine applications such as antibacterial agents, antifouling, wound healing, drug delivery, tissue engineering, and bone regeneration. They advanced the applications to be cheap, biocompatible, biodegradable, easy for shaping and processing into different forms, with suitable chemical, mechanical and physical properties.

Molecularly imprinted polymers (MIPs) have been widely used in nanomedicine during the last few years. However, their potential is limited by their intrinsic properties resulting, for instance, in lack of control in drug release processes or complex detection for in vivo imaging. Recent attempts in creating hybrid nanomaterials combining MIPs with inorganic nanomaterials succeeded in providing a wide range of new interesting properties suitable for nanomedicine. Through this review, we aim to illustrate how hybrids molecularly imprinted polymers may improve patient care with enhanced imaging, treatments and combination of both.

Galangin(Gal) is a natural active flavonoid compound separated from the roots and rhizomes of Alpinia ofcinarum Hance. Modern pharmacological studies have shown that Gal has a variety of biological activities such as anti-tumor, anti-fungal, anti-bacterial, anti-inflammatory, anti-ischemic stroke, suppressing vitiligo and Alzheimer’s disease, etc. The purpose of this research was to prepare a galangin self-microemulsion drug delivery system (Gal-SMEDDS) and compare its anti-oxidant activity and pharmacokinetics with free Gal.The average particle size of the prepared Gal-SMEDDS was approximately 21.33 nm, the polydispersity index was 0.096, the zeta potential was -4.09 mV, and the entrapment efficiency was 96.74%. Compared with free Gal, the release of Gal-SMEDDS was improved in vitro release experiment. Cell experiments showed that Gal had obvious anti-oxidation effect, and the effect of Gal-SMEDDS was better than that of free Gal. In vivo pharmacokinetic experiments showed that the pharmacokinetic parameters of Gal-SMEDDS were better than that of free Gal, which indicated that the self-microemulsion drug delivery system(SMEDDS) effectively increases the oral bioavailability of Gal and alters its pharmacokinetic parameters, such that it may be effective in the treatment of anti-oxidant.

Hydrogels obtained from the combination of different polymers are an interesting strategy for the development of controlled release system platforms and tissue engineering scaffolds. In this study, the applicability of sodium alginate-g-(QCL-co-HEMA) hydrogels for these biomedical applications was evaluated. Hydrogels were synthesized by free-radical polymerization using different concentration of the components. The hydrogels were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, and swelling degree; betamethasone release as well as the in vitro cytocompatibility with chondrocytes and fibroblast cells were also evaluated. Scanning electron microscopy confirmed the porous surface morphology of the hydrogels in all cases. The swelling percent was determined at different pH and was observed to be pH-sensitive. The controlled release behavior of betamethasone from the matrices was investigated in PBS media (pH = 7.4) and the drug was released in a controlled manner up to 8 h. Human chondrocytes and fibroblasts were cultured on the hydrogels. The MTS assay shown that almost all hydrogels are cytocompatibles and an increase the proliferation in both cell types after one week of incubation was observed by Live/Dead® assay. These results demonstrate that these hydrogels are attractive materials for pharmaceutical and biomedical applications due to their characteristics, their release kinetics and biocompatibility.

The delivery of Cytochrome c (Cyt c) to the cytosol stimulates apoptosis in cells were its release from mitochondria and apoptosis induction is inhibited. We developed a drug delivery system consisting of Cyt c nanoparticles decorated with folate-poly(ethylene glycol)-poly(lactic-co-glycolic acid)-thiol (FA-PEG-PLGA-SH) to deliver Cyt c into cancer cells and test their targeting in the Lewis Lung Carcinoma (LLC) mouse model. Cyt c-PLGA-PEG-FA nanoparticles (NPs) of 253 ± 55 and 354 ± 11 nm were obtained by Cyt c nanoprecipitation, followed by surface decoration with the co-polymer SH-PLGA-PEG-FA, and compared to a nanoparticle-free formulation. Overexpression of FA in LLC cells and internalization of Cyt c-PLGA-PEG-FA nanoparticles (NPs) was confirmed by confocal microscopy. Caspase activation assays show NPs retain 88-96% Cyt c activity. The NP formulations were more efficient in decreasing LLC cell viability than the NP-free formulation, with IC50: 49.2 to 70.1 μg/ml versus 129.5 μg/ml, respectively. Our NP system is thrice as selective towards cancerous than normal cells. In-vivo studies using tagged nanoparticles show accumulation in mouse LLC tumor 5 min post-injection. In conclusion, our NP delivery system for Cyt c shows superiority over the NP-free formulation and reaches a folic acid-overexpressing tumor in an immune-competent animal model.

Nanodiamonds of detonation origin are promising delivery agents of anti-cancer therapeutic compounds in a whole organism like mouse, owing to their versatile surface chemistry and ultra-small 5 nm average primary size compatible with natural elimination routes. However, to date, little is known about tissue distribution, elimination pathways and efficacy of nanodiamonds-based therapy in mice. In this report, we studied the capacity of cationic hydrogenated detonation nanodiamonds to carry active small interfering RNA (siRNA) in a mice model of Ewing sarcoma, a bone cancer of young adult due in the vast majority to the EWS-Fli1 junction oncogene. Replacing hydrogen gas by its radioactive analog tritium gas led to the formation of labeled nanodiamonds and allowed us to investigate their distribution throughout mouse organs and their excretion in urine and feces. We also demonstrated that siRNA directed against EWS-Fli1 inhibited this oncogene expression in tumor xenografted on mice. This work is a significant step to establish cationic hydrogenated detonation nanodiamond as an effective agent for in vivo delivery of active siRNA.

Owing to their unique physicochemical properties, nanoparticles are used in a variety of ways in the field of cancer treatment, including imaging, drug delivery, and photothermal and photodynamic therapies. The fascinating properties of nanoparticles are determined by their size, morphology, and constituent elements, and various synthetic methods and post-synthetic techniques have been applied to control these factors. Herein, we present examples of shape and composition control through galvanic replacement, a technique that exploits redox potential differences between elements to induce spontaneous ion-exchange and highlight its specific contributions to cancer treatment applications. The present article identifies the recent advances in nanoparticle formation techniques and discusses the future outlook of the field.

Elevated levels of oxidative stress in the corneal epithelium contribute to the progression of dry eye disease pathology. Previous studies have shown that antioxidant therapeutic intervention is a promising avenue to reduce disease burden and slow disease progression. In this study, we evaluated the pharmacological efficacy of Xanthohumol in preclinical models for dry eye disease. Xanthohumol is a naturally occurring prenylated chalconoid that promotes the transcription of phase II antioxidant enzymes. Xanthohumol exerted a dose-response in preventing tert-butylhydroxide-induced loss of cell viability in human corneal epithelial (HCE-T) cells and resulted in a significant increase in expression of nuclear factor erythroid 2-related factor 2 (Nrf2), the master regulator of the endogenous antioxidant system. Xanthohumol-encapsulating poly(lactic-co-glycolic acid) nanoparticles (PLGA NP) were cytoprotective against oxidative stress in vitro, and significantly reduced corneal fluorescein staining in the mouse desiccating stress/ scopolamine model for dry eye disease in vivo by reducing oxidative stress-associated DNA damage in corneal epithelial cells. PLGA NP represent a safe and efficacious drug delivery vehicle for hydrophobic small molecules to the ocular surface. Optimization of NP-based antioxidant formulations with the goal to minimize instillation frequency may represent future therapeutic options for dry eye disease and related ocular surface disease.

The development of targeted therapeutics for cancer continues to receive intense research attention as laboratories and pharmaceutical companies seek to develop drugs and technologies that improve treatment efficacy and mitigate harmful side effects. In the aftermath of World War I, it was discovered that mustard gas destroys rapidly dividing cells and could be used to treat cancer. Since then, chemotherapy has remained a predominant treatment for cancer; however, the destruction of dividing cells throughout the body yields devastating side effects including off-target damage of the digestive tract, bone marrow, skin, and reproductive tract. Furthermore, the high mutation rate of cancerous cells often renders chemotherapy ineffective long-term. Therapies with improved specificity, localization, and efficacy are redefining cancer treatment. Herein, we define and summarize the principal advancements in targeted cancer treatment and briefly comment on the march towards personalized medicine in the treatment of human cancer.

The dynamic interaction between carbon nanodots (CNDs) and cannabidiol (CBD) has captured significant attention as an innovative avenue for redefining drug delivery and amplifying therapeutic effectiveness. This in-depth review delves into the intricate synergy between these two elements, unveiling their profound potential in medicine. Commencing with an examination of the unique characteristics of CNDs and the techniques governing their synthesis, we discuss their versatility as drug carriers, highlighting their invaluable role in advancing CBD delivery. Cannabidiol, a non-psychoactive compound sourced from cannabis, has emerged as a focal point for its diverse therapeutic attributes. Nevertheless, the limitations posed by its restricted bioavailability and susceptibility to degradation pose substantial hindrances to realizing its full potential. Here, we elucidate how the amalgamation of CBD with CNDs transcends these challenges. We delve into the mechanisms that underlie this synergy, such as the augmentation of solubility and the safeguarding of CBD against premature breakdown, providing an intricate analysis. We will also journey you through a comprehensive exploration of diverse CBD loading techniques onto CNDs, dissecting the realms of physical encapsulation, covalent bonding, and adsorption processes. In summation, the combination of CNDs and CBD presents an extraordinary opportunity to elevate therapeutic outcomes. This synergetic paradigm masterfully tackles pivotal challenges in drug delivery, thereby paving the path for pioneering medical solutions.

The topography and chemical composition modification of the titanium (Ti) implants play a decisive role in improving biocompatibility and bioactivity, accelerating osseointegration, and, thus, determining clinical success. In spite of the development of surface modification strategies, bacterial contamination is a common cause of failure. The use of systemic antibiotic therapy does not guarantee action at the contaminated site. In this work, we proposed a surface treatment for Ti implant that aim to improve its osseointegration and reduce bacterial colonization in surgery site due to local release of antibiotic. The Ti disks were hydrothermally treated with 3M NaOH solution to form a nanostructured layer of titanate on the Ti surface. Metronidazole was impregnated on these nanostructured surfaces to allow its local release. The samples were coated with poly(vinyl alcohol) - PVA films with different thickness to evaluate a possible control of drug release. Gamma irradiation was used to crosslink the polymer chains leading to a hydrogel layer formation and to sterilize the samples. The samples were characterized by XRD, SEM, FTIR, contact angle measurements, “in vitro” bioactivity, and drug release analysis. The alkaline hydrothermal treatment successfully produced intertwined, web-like nanostructures on the Ti surface, providing wettability and bioactivity to Ti samples (Ti+TTNT samples). Metronidazole was successfully loaded and released from Ti+TTNT samples coated or not with PVA. Although the polymeric film acted as a physical barrier to drug delivery, all groups reached the minimum inhibitory concentration for anaerobic bacteria. Thus, the surface modification method presented is a potential approach to improve the osseointegration of the Ti implant and to associate local drug delivery to dental implants, preventing early infections and bone failure.

Plantago major L. is a worldwide available plant that has been used traditionally for several medical application due to its properties such as wound healing, anti-inflammatory, antimicrobial etc. This work aimed to develop and evaluate nanostructured PCL electrospun dressing with P. major extract encapsulated in nanofibers for application in wound healing. The extract from leaves was obtained by extraction in a mixture of water:ethanol= 1:1 of the freeze-dried extract presented a minimum inhibitory concentration (MIC) for Staphylococcus Aureus susceptible and resistant to methicillin of 5.3 mg/mL, a high antioxidant capacity, but a low content of total flavonoids. Electrospun mats without defects were successfully produced using two P. major extract concentrations based on MIC value. The extract incorporation in PCL nanofibers was confirmed by FTIR and contact angle measurements. The PCL/P. major extract was evaluated by DSC and TGA demonstrating that incorporation of the extract decreases the thermal stability of the mats as well as the degree of crystallinity of PCL-based fibers. The P. major extract incorporation on electrospun mats produced a significant swelling degree (more than 400%) and increased the capacity of adsorbing wound exudates and moisture, important characteristics for skin healing. The extract-controlled release evaluated by in vitro study in PBS (pH, 7.4) shows that P. major extract delivery from the mats occurs in the first 24 h, demonstrating their potential capacity to be used in wound healing.

Magnetic Nanoparticles (MNPs) is a promising technique to cure brain diseases. On the one hand, by serving as drug carriers, they can bypass the blood-brain barrier and deliver drug molecules to the brain parenchyma; on the other hand, their transport trajectory can be manipulated by applying an external magnetic field. However, due to the complex microstructure of brain tissues, e.g. the anisotropy of white matter (WM), how to achieve desired drug distribution patterns, e.g. uniform distribution, by tuning the drug delivery system is largely unknown. Here, in this study, by adopting a mathematical model capable of capturing the diffusion trajectories of MNPs in the microstructures, we systematically investigated the effects of key parameters in the MNPs delivery system on the equivalent diffusion coefficient of MNPs in the microenvironment of brain WM. The results show that uniform distribution of MNPs in anisotropic tissues can be achieved by adjusting the particle size and magnetic field. We have not only obtained a deeper understanding on how to optimise the MNPs delivery system, it can also be anticipated that an improved mathematical model could even help to achieve complex drug distribution patterns in the complicated brain environment by designing an appropriate combination of the key parameters.

One of the most frequent brain diseases, Alzheimer's is defined by poor cognitive function brought on by the build-up of Beta Amyloid plaques and the gradual death of neurons. Glucose metabolism and the development of amyloid plaques are being studied together. Under physiologically normal circumstances, glucose is the primary substrate for the adult human brain. The prodromal phases of AD are significantly influenced by glucose hypometabolism. Hypometabolism of glucose in the brain is a clear sign of mitochondrial dysfunction and bioenergetic system impairment. By regulating energy synthesis and cell death, mitochondria play a crucial role in the functioning of cells. Increased formation of reactive oxygen species (ROS) and oxidative stress are a result of mitochondrial dysfunction, which also accelerates the development of Alzheimer's disease. For the maintenance of balance, autophagy is crucial because it selectively destroys damaged mitochondria. AD affects this route for mitochondrial breakdown. Targeting specific mitochondrial ligands by interventions along this pathway might be a useful therapeutic approach. Due to a number of biological obstacles, this method has significant limitations. As a result, many nanocarriers have been created to improve drug delivery effectiveness. All potential nanotechnology-based treatments for AD have been examined in this study, with a particular emphasis on medication delivery to the mitochondria

In this work, polyacrylic acid-functionalized MCM-41 was synthesized, which was further interacted with calcium ions, to realize enhanced pH-responsive nanocarrier for sustained drug release. First, mesoporous silica nanoparticles (MSNs) were prepared by the sol-gel method. Afterward, (3-trimethoxysilyl)propyl methacrylate (TMSPM) modified surface was prepared by using the post-grafting method, then polymerization of acrylic acid was proceeded. After adding calcium chloride solution, polyacrylic acid-functionalized MSNs with calcium-carboxyl ionic bonds in the polymeric layer, which can prevent the cargo from leaking out of the mesopore, were prepared. The structure and morphology of the modified nanoparticles (PAA-MSNs) were characterized by X-ray diffraction (XRD), Fourier-transform infrared (FT-IR) spectroscopy, transmission electron microscopy (TEM), and N2 adsorption-desorption analysis, etc. The controlled release of guest molecules was studied by using 5-fluorouracil (5-FU). The drug molecules-incorporated nanoparticles showed different releasing rates under different pH conditions. It is considered that our current materials have the potential as pH-responsive targeted nanocarriers in the field of medical treatment.

Lipid nanoparticles have an interesting part of drug delivery system. In this study, the modification of the convention nano-lipid based soybean lecithin was demonstrated. Ginger oil derived Zingiber officinale was used along with lecithin, cholesterol and span 80 to fabricate nano-lipid (GL nano-lipid) using thin-film method. Through TEM and confocal microscope, GL nano-lipid exposes the liposome- like morphology. The average size of the resultant nanoparticles was 249.1nm with monodistribution (PDI= 0.021). The ζ-potential of GL nano-lipid was negative as similar to as prepared nano-lipid based lecithin. GL nano-lipid express the highly stable over 60 days of storage at room temperature in term of size, ζ-potential. A shift of pH value from alkaline to acid was detected in lecithin nano-lipid, while with the incorporation of ginger oil, pH value of nano-lipid dispersion was around 7.0. Furthermore, due to the rich of shogaol-6 and other active compounds in ginger oil, the GL nano-lipid is endowed with intrinsic antibacterial feature. In addition, the sulforhodamine B (SRB) assay and live/dead imaging revealed the excellent biocompatibility of GL nano-lipid. Notably, GL nano-lipid was capable to carry the hydrophobic agents as curcumin and perform a pH-dependent release profile. A subsequent characterization are a suitable potential for drug delivery system.

Dry powder inhalers are used by a large number of patients worldwide to treat respiratory diseases. The objective of this work is to experimentally investigate changes in aerosol particle diameter and particle number concentration of pharmaceutical aerosols generated by five dry powder inhalers under realistic inhalation and exhalation conditions. The active respiratory system model (xPULM™) was used as a model of the human respiratory system and to simulate a patient undergoing inhalation therapy. A mechanical upper airway model was developed, manufactured and introduced as a part of the xPULM™ to represent the human upper respiratory tract with high fidelity. Integration of optical aerosol spectrometry technique into the setup allowed for evaluation of pharmaceutical aerosols. The results show that the upper airway model increases the resistance of the overall system and act as a filter for bigger particles (>3 µm). Furthermore, there is a significant difference (p < 0.05) in mean particle diameter between inhaled and exhaled particles with the majority of the particles depositing in the lung. The minimum deposition is reached for particle size of 0.5 µm. The mean particle number concentrations exhaled are 2.94% (BreezHaler®), 2.66% (Diskus®), 10.24% (Ellipta®) 2.13% (HandiHaler®) and 6.22% (Turbohaler®). In conclusion, the xPULM™ active respiratory system model is a viable option for studying interactions of pharmaceutical aerosols and the respiratory tract in terms of applicable deposition mechanisms. The model can support the reduction of animal experimentation in aerosol research and provide an alternative to experiments with human subjects.

Chitosan arouses large interest due to its properties and possible applications. Every year the number of publications and patents based on this polymer increases. Chitosan exhibits poor solubility in neutral and basic media limiting its use in such conditions. Another serious obstacle is directly related to its natural origin. Chitosan is not a single polymer with a defined structure but a family of molecules with differences in their composition, size, and monomer distribution. These properties have a fundamental effect on the biological and technological performance of the polymer. Moreover, some of the biological properties claimed are discrete. In this review, we discuss how chitosan chemistry can solve the problems related to its poor solubility and can boost the polymer properties. We focus on some of the main biological properties of chitosan and the relationship with the physicochemical properties of the polymer. Then, we visit two polymer applications related to green processes: the use of chitosan in the green synthesis of metallic na-noparticles and its use as support in biocatalyst. Finally, we briefly describe how making use of the technological properties of chitosan it is possible to develop a variety of systems for drug delivery

In this work, we designed and fabricated a multifunctional nanocomposite system which consists of chitosan, raspberry-like silver nanoparticles and graphene oxide. Room temperature atmospheric pressure microplasma (RT-APM) process provides a rapid, facile, and environment-friendly method for introducing silver nanoparticles into the composite system. By loading different drugs onto the polymer matrix and/or graphene oxide, our composite can achieve a pH controlled dual drug release with release profile specific to the drugs used. In addition to its strong antibacterial ability against E. coli and S. aureus, our composite also demonstrates excellent photothermal conversion effect under irradiation of near infrared lasers. These unique functionalities point to it’s the potential of nanocomposite system in multiple applications areas such as multimodal therapeutics in healthcare, water treatment, and anti-microbial, etc.

Doxorubicin, a member of the anthracycline family, is a common anticancer agent often used as a first line treatment for the wide spectrum of cancers. Doxorubicin-based chemotherapy, although effective, is associated with serious side effects, such as irreversible cardiotoxicity or nephrotoxicity. Those often life-threatening adverse risks, responsible for the elongation of the patients' recuperation period and increasing medical expenses, have prompted the need for creating novel and safer drug delivery systems. Among many proposed concepts, polymeric nanocarriers are shown to be a promising approach, allowing for controlled and selective drug delivery simultaneously enhancing its activity towards cancerous cells and reducing toxic effects on healthy tissues. This article is a chronological examination of the history of the work progress on polymeric nanostructures, designed as efficient doxorubicin nanocarriers, with the emphasis on the main achievements of 2010-2020. Numerous publications have been reviewed to provide an essential summation of the nanopolymer types and their essential properties, mechanisms towards efficient drug delivery, as well as active targeting stimuli-responsive strategies that are currently utilized in the doxorubicin transportation field.

Polyhydroxyalkanoate (PHA) co-polymers show relatively higher in vivo degradation rate compared to other PHAs thus they received a great deal of attention for a wide range of medical applications. Nanoparticles (NPs) loaded with poorly water soluble anticancer drug docetaxel (DCX) were produced using poly 3-hydroxybutyrate-co-4-hydroxybutyrate, P(3HB-co-4HB), co-polymers biosynthesised from Cupriavidus sp. USMAA1020 isolated from Malaysian environment. Three co-polymers with different molar proportions of 4-hydroxybutirate (4HB) were used: 16% (PHB16), 30% (PHB30) and 70% (PHB70) 4HB-containing P(3HB-co-4HB). Blank and DCX loaded nanoparticles were then characterized for their size and size distribution, surface charge, encapsulation efficiency and drug release. Pre-formulation studies showed that an optimised formulation could be achieved through the emulsification/solvent evaporation method using PHB70 with the addition of 1.0% PVA, as stabilizer and 0.03% VitE-TPGS, as surfactant. DCX-loaded PHB70 nanoparticles (DCX-PHB70) gave the desired particle size distribution in term of average particles sizes around 150 nm and narrow particle size distribution (PDI below 0.100). The encapsulation efficiencies result showed that at 30% w/w drug-to-polymer ratio: DCX- PHB16 NPs were able to encapsulate up to 42% of DCX; DCX-PHB30 NPs encapsulated up to 46% of DCX and DCX-PHB70 NPs encapsulated up to 50% of DCX within the nanoparticles system. Approximately 60% of DCX was released from the DCX-PHB70 NPs within 7 days for 5%, 10% and 20% of drug to polymer ratio while for the 30% and 40% drug to polymer ratios, an almost complete drug release (98%) after 7 days of incubation was observed.

In recent years, polyureas with dynamic hindered urea bonds (HUBs), as a class of promising biomedical polymers, have attracted attention as a benefit of their controlled hydrolytic property. The effect of the chemical structures on the properties of polyureas and their assemblies was rarely reported. In this study, four kinds of polyureas with different chemical groups have been synthesized, and the polyurea from cyclohexyl diisocyanate and tert-butyl diamine showed the fastest hydrolytic rate. The amphiphilic polyurea composed of hydrophobic cyclohexyl-tert-butyl polyurea and hydrophilic poly(ethylene glycol) was synthesized for controlled delivery of antitumor drug paclitaxel (PTX). The PTX-loaded PEGylated polyurea micelle more effectively entered into the murine breast cancer 4T1 cells and inhibited the corresponding tumor growth in vitro and in vivo. Therefore, the PEGylated polyurea with adjustable degradation might be a promising polymer matrix for drug delivery.

Antimicrobial peptides (AMPs) have emerged as a promising solution to tackle bacterial infections and combat antibiotic resistance. However, their clinical application has been hindered by their vulnerability to protease degradation and toxicity towards mammalian cells. To overcome these challenges, our study aims to develop a method to enhance the stability and safety of AMPs, applicable to effective drug-device combination products. KR12 antimicrobial peptide was chosen and in order to further enhance its delivery and efficacy, HIV TAT protein-derived cell-penetrating peptide (CPP) was fused to form CPP-KR12. A new product, CPP-KR12@Si, was developed by forming silica nanoparticles with self-entrapped CPP-KR12 peptide using the biomimetic silica precipitability due to its cationic nature. Peptide delivery from CPP-KR12@Si to bacteria and cells was delivered at a slightly delayed rate with improved stability against trypsin treatment and a reduction in cytotoxicity over CPP-KR12. Finally, the antimicrobial potential of CPP-KR12@Si/bone graft substitute (BGS) combination product was demonstrated, which is coated with CPP-KR12 in the form of nanoparticles on the surface of BGS. Self-entrapped AMP in silica nanoparticles is a safe and effective AMP delivery method that will be useful for developing a drug/device combination product for tissue regeneration.

There are dozens of approved, investigational and experimental antiviral agents. Many of these agents cause serious side effects, which can be revealed only after drug administration. Identification of the side effects prior to drug administration is challenging. Here we describe an ex vivo approach for studying immuno- and neuro-modulatory properties of antiviral agents, which could be associated with potential side effects of these therapeutics. The approach combines drug toxicity/efficacy tests and transcriptomics, which is followed by cytokine and metabolite profiling. We demonstrated the utility of this approach with several examples of antiviral agents. We also showed that the approach can utilize different immune stimuli and cell types. It can also include other omics techniques, such as genomics and epigenomics, to allow identification of individual markers associated with adverse reactions to antivirals with immuno- and neuro-modulatory properties.

For 80 years high-intensity focused ultrasound (HIFU) has been a significant area for medical research. It is a non-invasive procedure which causes cell death in a highly localised area at a defined distance from the transducer. Since 2000, the clinical indications have broadened considerable as the technology has improved. This review looks back at the history of HIFU and the current clinical indications.

Nanoencapsulation has emerged as a recent improvement in the delivery of drugs, offering and improving stability and bioavailability, and allowing for the controlled and targeted delivery of substances to specific cells or tissues. However, traditional nanoparticle delivery faces challenges such as short circulation time and immune recognition. To address these issues, cell membrane-coated nanoparticles have been proposed as a promising alternative. The production of cell membrane-coated nanoparticles involves three key stages: cell lysis and membrane fragmentation, membrane isolation, and nanoparticle coating. Typically, cell membranes are fragmented using hypotonic lysis in combination with homogenization or sonication. Subsequent membrane fragments are isolated through multiple centrifugation steps. The coating of nanoparticles can be achieved through extrusion, sonication, or a combination of both methods. This analysis shows the absence of a universally applicable method for nanoparticle coating, as the three stages exhibit notable differences in their procedures. Here we review ongoing developments and approaches to cell membrane-coated nanoparticles that position this technology as a promising alternative for effective targeted drug delivery and many other therapeutic applications.

This article discusses the fabrication of pullulan/polyvinyl alcohol (PVA) and PVA blends as carrier polymers for drug delivery. This study utilized coaxial electrospinning to encapsulate doxorubicin (DOX), a common anticancer drug, within nanofibers, which helped mitigate the adverse effects of DOX on normal cells. The study also demonstrated that the coaxial electrospinning technique using PVA/pullulan cores was effective in inhibiting the attachment and proliferation of HeLa cells, a type of cervical cancer cell. The use of pullulan/PVA and PVA blends as carrier polymers in conjunction with coaxial electrospinning could provide a safe and effective drug delivery system for the treatment of cervical and other solid malignancies. The study concluded that nanofibers showed promising results in inhibiting the growth of HeLa cells, indicating their potential as safe and effective drug delivery systems for treating cervical cancer and other solid malignant tumors.

Worldwide, hypoxia-related conditions, including cancer, COVID-19, and neuro-degenerative diseases, often lead to multi-organ failure and significant mortality. Oxygen, crucial for cellular function, becomes scarce as levels drop below 10 mmHg (<2% O2), triggering mitochondrial dysregulation and activating hypoxia-induced factors (HiFs). Herein, Oxygen nanoBubbles (OnB), an emerging versatile oxygen de-livery platform, implies to offer a novel approach to address hypoxia-related pathologies. This review explores OnB oxygen delivery strategies and systems, including diffusion, ultrasound, photodynamic, and pH-responsive nanobubbles. It delves into the nanoscale mechanisms of OnB, elucidating their role in mitochondrial metabolism (TFAM, PGC1alpha), hypoxic responses (HiF-1alpha), and their interplay in chronic pathologies including cancer and neurodegenerative disorders, amongst others. By understanding these dynamics and underlying mechanisms, this article aims to contribute to our accruing knowledge of OnB and the developing potential in ameliorating hypoxia- and metabolic stress-related conditions and fostering innovative therapies.

Leukemia, characterized by abnormal blood cell proliferation, remains a significant challenge in cancer treatment. Thymoquinone (TQ), a bioactive compound derived from black seed, has demonstrated anticancer properties, including telomerase inhibition and induction of apoptosis. However, TQ's poor solubility and limited bioavailability hinder its clinical application. This study explores the use of SBE-β-CD, a cyclodextrin derivative, to enhance the solubility and stability of TQ for leukemia treatment. SBE-β-CD offers low hemolytic activity and has been successfully employed in controlled drug release systems. The study investigates the formation of inclusion complexes between TQ and SBE-β-CD and assesses their effects on leukemia cell growth. Results indicate that the TQ/SBE-β-CD complex exhibits improved solubility and enhanced cytotoxic effects compared to TQ alone, suggesting the potential of SBE-β-CD as a drug delivery system for TQ. Annexin V-FITC tests demonstrate increased apoptosis and reduced telomerase activity in leukemia cells treated with TQ/SBE-β-CD, supporting its anti-leukemic potential. Molecular docking analysis reveals a strong binding affinity between TQ and telomerase. However, further research is needed to optimize the apoptotic effects and minimize necrosis induction. In conclusion, TQ/SBE-β-CD shows promise as a novel strategy for leukemia treatment by targeting telomerase and enhancing the cytotoxic effects of TQ, offering a potential solution to overcome the limitations of TQ's poor solubility and bioavailability.

Bacterial infections are a constant challenge in the management of acute and chronic wounds. Chronic wounds, like diabetic foot ulcers, have increased significantly in the last years due to the rise of an aging population. A better understanding of the infectious pathophysiological mechanisms is urgently needed along with new options for the treatment of wound infections and wound healing disorders. New advances in the preparation of biocompatible dressing materials that can be loaded with antimicrobial drugs may improve the topical treatment of infected wounds. In this study, we investigated the antimicrobial activity of polyvinylpyrrolidone (PVP) foils loaded with ciprofloxacin (Cipro-foils) in the presence of acetic acid as co-solvent. We used ex vivo human wounds that were infected with two bacterial strains: Methicillin-Resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa (PAO1). The effectiveness of the treatment was demonstrated by the quantification of the living bacteria extracted from the wound and the detection of released immunological mediators in skin extracts and in the skin culture media. We found that Cipro-foils effectively treated the infection with both PAO1 and MRSA. Other than PAO1, MRSA had not proteolytic effects. MRSA infections increased cytokines expression and release. Interestingly, treatment with Cipro-foils could partially counteract these effects.

Due to their increased surface area, extent of swelling and active substance loading capacity and flexibility, nanogels made from natural and synthetic polymers have gained significant interest in the scientific and industrial areas. Especially, customized design and implementation of non-toxic, biocompatible, and biodegradable micro/nano carriers makes their usage very feasible for a range of biomedical applications, including drug delivery, tissue engineering, and bioimaging. The design and application methodologies of nanogels have been outlined in this review. Additionally, the most recent advancements in nanogel biomedical applications have been discussed, with a particular emphasis on applications for the delivery of drugs and biomolecules.

The purpose of this study is to develop and evaluate a self-microemulsifying drug delivery system (SMEDDS) to improve the oral absorption of poorly water-soluble Olaparib. Through the solubility test of Olaparib in various oils, surfactants and co-surfactants, pharmaceutical excipients for use in SMEDDS manufacturing were selected. Self-emulsifying regions were identified by mixing the selected materials at various ratios, and a pseudoternary phase diagram was constructed by synthesizing these results. Various physicochemical properties of microemulsion incorporating Olaparib were confirmed by investigating the particle morphology, particle size, zeta potential, drug content and stability. In addition, the improved dissolution and oral absorption of Olaparib were also confirmed through a dissolution test and a pharmacokinetic study. An optimal microemulsion was generated in the formulation of Capmul MCM EP/NF 10%, Labrasol 80% and PEG 400 10%. Fabricated nano-sized microemulsions were well-dispersed in aqueous solutions, and it was also confirmed that it was maintained well without any problems of either physical or chemical stability. The 5 min initial dissolution of Olaparib in fabricated formulations was improved by 10.6 times (pH1.2), 14.8 times (pH6.8) and 14.8 times (distilled water) compared to the values of Olaparib powder. The dissolution at 120min was 45.4±4.0%(pH1.2), 53.5±1.1% (pH6.8) and 58.1±1.00% (distilled water) in Olaparib powder but has been significantly improved by 1.7 times (74.8±1.9%), 1.6 times (84.2±0.3%) and 1.5 times (81.2±0.7%) in SMEDDS. Associated with the high dissolutions of Olaparib in fabricated microemulsions, the pharmacokinetic parameters were also greatly improved. The Cmax and AUCinf of Olaparib in the prepared microemulsion were increased 4.2- and 3.2-fold, respectively, compared to powder. Taken together with the results mentioned above, the microemulsion system could be an effective tool as an oral delivery formulation for Olaparib. Additionally, our results demonstrate that the SMEDDS systems comprising Capmul MCM, Labrasol and PEG 400 could be a useful option for improvement of several other poorly water-soluble drugs with physico-chemical properties similar to Olaparib.

Mesenchymal stem cells (MSCs) have the tumor-homing capacity, and therefore MSCs are considered to be a promising drug delivery carrier for cancer therapy. To maintain the viability and activity of MSCs, anti-cancer drugs are preferably modified on the surface of MSCs, rather than directly introduced into MSCs. In this study, we attempted to construct surface-modified MSCs with liposomes as a drug carrier by using magnetic anionic liposome/atelocollagen complexes we previously developed. We observed that large-sized magnetic anionic liposome/atelocollagen complexes were abundantly associated with MSCs via electrostatic interactions under a magnetic field, and its cellular internalization was lower than that of the small-sized complexes. Moreover, the complexes with higher atelocollagen concentration showed lower cellular internalization than the complexes with lower atelocollagen concentration. Based on these results, we succeeded in the efficient surface modification of MSCs with liposome by using large-sized magnetic anionic liposomes complexed with high concentration of atelocollagen. The constructed liposome-modified MSCs showed comparable proliferation rate and differentiation potential to unmodified MSCs. Furthermore, liposome-modified MSCs efficiently adhered to vascular endothelial cells and migrated toward the conditioned medium from cancer cells in vitro. These findings suggest that liposome-modified MSCs could serve as an efficient cell-based drug carrier for tumor targeted delivery.

Background: Current drug for the treatment of endometriosis is not able of completely cure and significant side effects hinder the continuation of treatment. So, the search for new drug candidates is necessary, and the use of plants extracts is highlighted. Babassu oil and copaiba oilresin have several therapeutic properties. We investigated the in vitro effects of two nanoemulsions containing babassu oil (Orbignya speciosa) (SNEDDS-18) and/or copaiba oilresin (Copaifera langsdorffii) (SNEDDS-18/COPA) on cultured human eutopic endometrium stromal cells from endometrial biopsies of patients without (CESC) and with (EuESC) endometriosis, and human stromal cells from biopsies of endometriotic lesions (EctESC). Methods: CESC, EuESC and EctESC were established and treated with SNEDDS-18 and SNEDDS-18/COPA to evaluate its effects on cytotoxicity, cell morphology, proliferation, and signaling pathways. Results: After 48 hours incubation with SNEDDS-18 and SNEDDS-18/COPA, cell viability and proliferation were inhibited, especially in EctESC. The lowest concentration of both nanoemulsions reduced cell viability and proliferation and breakdown the cytoskeleton in EctESCs. After 24h treatment it was observed a decrease in IL-1, TNF-α, and MCP-1, and an increase in IL-10 production. Conclusions: Both nanoemulsions can affect the endometriotic stromal cell behaviors, thus revealing two potential candidates for new phytotherapeutic agents on the management of endometriosis.

Anthocyanins are among the best-known phenolic compounds and possess remarkable biological activities, including antioxidant, anti-inflammatory, anticancer, and antidiabetic effects. Despite their therapeutic benefits, they are not widely used as health-promoting agents due to their insta-bility, low absorption, and thus, low bioavailability and rapid metabolism in the human body. Recent research suggests that the application of nanotechnology could increase their solubility and/or bioavailability, and thus, their biological potential. Therefore, in this review, we decided to provide, for the first time, a comprehensive overview of in vitro and in vivo studies on nanocarriers used as delivery systems of anthocyanins, and their aglycones, i.e., anthocyanidins alone or com-bined with conventional drugs to the treatment or management of chronic diseases.