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Polymer technology has rapidly advanced across diverse domains, particularly in biomedical applications. Among various polymers, polyurethane (PU) hold great potential in developing biomaterials such as biomedical scaffold and drug delivery. In this study, we have innovatively engineered eco‐friendly polyurethane using lignin, a sustainable bio‐polyol derived from oil palm empty fruit bunches. To enhance the physicochemical properties of the PU, we have incorporated hydroxyapatite (HA) into the composites. The inclusion of HA has led to notable improvements in crucial properties such as density, porosity, and water absorption, making these composites ideal candidates for tissue regeneration scaffolds. Furthermore, to assess their biomedical applicability in drug delivery and cell scaffolding, we have employed the quercetin drug model. The results revealed a sustained kinetic release behavior within the polyurethane/hydroxyapatite (PU/HA) composites, showcasing their potential for controlled drug delivery applications. Moreover, cytotoxicity assays conducted using neuro‐2a cell models demonstrated the non‐cytotoxic nature of both PU and PU/HA composites. This finding holds significant implications for biomedical applications, indicating that these composites offer biocompatible platforms for tissue engineering and regenerative medicine endeavors. The ability of these composites to support cell viability underscores their potential for a wide range of biomedical applications, including neural tissue engineering and drug delivery systems targeting brain diseases. These findings pave the way for the development of innovative and sustainable biomaterials with diverse biomedical applications. Highlights: An eco‐friendly polyurethane has been engineered by harnessing liginin‐derived oil palm empty fruit bunches.Incorporation of hydroxyapaptite enhance the physical properties of polyurethane.Controlled kinetic drug release is one of polyurethane/hydroxyapatite (PU/HA) composites features.The PU/HA composites has low cytotoxicity against neuro‐2a cells. [ABSTRACT FROM AUTHOR]

The AgNPs‐Rsvl complex was investigated for its anti‐cancer effects on human breast cancer cell lines. The UV–vis spectrophotometer was used to perform synthesized AgNPs‐Rsvl binding analyses. The size and morphology of the AgNPs were determined by field emission gun‐transmission electron microscopy (FEG‐TEM). The surface chemical signatures of AgNPs nanocomposites were assessed using FT‐IR spectroscopy, and the zeta potential (ζ potential) of various AgNPs colloids was measured using the Zetasizer Nano ZS analyzer. Cell proliferation was analyzed using the XTT method and cell apoptosis was analyzed using the AnnexinV‐fluorescein isothiocyanate (FITC)/PI method. The effects of resveratrol were evaluated on human breast cancer cell lines (MDA‐MB‐231 and MCF‐7). As a result of flow cytometry, a decrease in viability was observed in the MDA‐MB‐231 cells, and an increase in early apoptotic, late apoptotic, and necrotic values was observed. Resveratrol arrests the cell cycle in the G0/G1 phase but when used with AgNPs, the cell cycle arrests at the S phase. The combination of resveratrol and AgNPs exhibited a cytotoxic effect on cancer cells, with MDA‐MB‐231 breast cancer cells being the most sensitive to AgNPs‐Rsvl. Resveratrol and AgNPs arrested the cell cycle and increased apoptosis, indicating their potential use in breast cancer treatment. [ABSTRACT FROM AUTHOR]

It is hypothesized that layer-by-layer acetate-coated Paclitaxel-loaded PLGA nanoparticles (F2) can be engineered to potentiate the effectiveness of Paclitaxel (PTX) on LNCaP, a human prostate cancer cell line. The core of the layer-by-layer NPs is formed by nanoprecipitation, and the shell of the NPs is engineered using the sodium acetate's unique coating mechanism and surface-active properties. The resulting nanoformulation physicochemical properties are characterized by Fourier Transform Infra-Red (FTIR), Differential Scanning Calorimetry (DSC) Transmission Electron Microscopy (TEM), NanoSight NS300, spectrophotometry, Korsmeyer-Peppas model, respectively. The NP's cytotoxicity on LNCaP is assessed by MTS assay. The DSC and the FTIR confirm SA's coating of the NPs. The particle's mean diameters (PMD) are 89.4±2.3- to 114.4±7.6 nm. The TEM shows a unique multilayer and spherical nanoparticle. The encapsulation efficiency of commonly PTX-loaded PLGA NPs (F1) and F2 are 84.37±2.71% and 86.74±2.22, respectively. The drug transport mechanism of F1 and F2 is anomalous transport and case II, respectively. F2 follows a zero-order release mechanism. The cell viability is 45.08±2.18% and 60.17±4.72% when LNCaP is treated with 10 µg/mL of F2 and F1, respectively, after 48 hours of exposure. F2 and F1 cell growth inhibition are dose-dependent. This unique process of engineering the layer-by-layer NPs will provide new horizons for developing future innovative nanoparticles for targeted prostate cancer therapy. [Display omitted] • Layer-by-layer nanoparticles are engineered using a modified nanoprecipitation method and sodium acetate's unique surface-active and coating properties. • The drug transport mechanism of the layer-by-layer nanoparticle is case II and follows a zero-order release mechanism. • A low dose of layer-by-layer nanoparticles produces potent cytotoxicity. • The layer-by-layer nanoparticle will provide new horizons for developing targeted prostate cancer therapy nanoparticles. [ABSTRACT FROM AUTHOR]

Complex by DDMC/sncRNAs(a-miR-155, piR-30074, and miR-125b) have shown the full recovery of mice from virus-induced sarcoma after treatment by changing to normal cells from cancer cells. With kinetic of inhibiting tumor growth, the difference from control (m m 2) of one intravenous injection and two intravenous injections is the same curvature and rate so that this is a soliton wave having a permanent form (velocity, shape) such as one faster soliton overcoming another one without any changing shape in the case of two intravenous injections. Signal transduction for this DDS must be Hill-type sigmoids following the nonlinear Schrödinger model by transfer of energy, sine-Gordon soliton model by momentum, and Fisher KPP soliton model by mass transfer. We find out that the cell outlet/inlet response of DDMC/sncRNAs is more dependent on the soliton signal not losing energy and shape without jamming communication. The endoplasmic reticulum-mitochondrial C a 2 + fluxes induced by soliton to Chromosome in nuclear will take place epigenetic modifications on 5-position of cytosine (5mC) by TET enzymes and thymine DNA glycosylase (TDG) as an overall intracellular reaction. By soliton flow, the result shows the equations of quantum mechanics can be related to the epigenetic control with C a 2 + fluxes followed by "induced fit model" Hill equation S-shaped. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases have been the leading cause of global mortality and disability. In addition to traditional drug and surgical treatment, more and more studies investigate tissue engineering therapeutic strategies in cardiovascular medicine. Collagen interweaves in the form of trimeric chains to form the physiological network framework of the extracellular matrix of cardiac and vascular cells, possessing excellent biological properties (such as low immunogenicity and good biocompatibility) and adjustable mechanical properties, which renders it a vital tissue engineering biomaterial for the treatment of cardiovascular diseases. In recent years, promising advances have been made in the application of collagen materials in blood vessel prostheses, injectable cardiac hydrogels, cardiac patches, and hemostatic materials, although their clinical translation still faces some obstacles. Thus, we reviewed these findings and systematically summarizes the application progress as well as problems of clinical translation of collagen biomaterials in the cardiovascular field. The present review contributes to a comprehensive understanding of the application of collagen biomaterials in cardiovascular medicine. [ABSTRACT FROM AUTHOR]

Sodium alginate (AlgNa) is often used to prepare oral drug capsules, offering the advantages of facile carrier formation and pH sensitivity. However, these capsules suffer from high porosity, large pore size, and mechanical and physiological instabilities. Although the performance of AlgNa in oral drug carriers can be enhanced through hybridization with other substances, this results in increased complexity and additional preparation steps. To address this problem, organic–inorganic hybrid capsules are herein prepared via the one‐step incorporation of aminosilanes (3‐aminopropyltriethoxysilane and 3‐(2‐aminoethylamino)propyltrimethoxysilane) into AlgNa and evaluated as delivery vehicles for the sustained release of a model drug, diclofenac sodium. The hybrid capsules show elevated drug encapsulation efficiencies (up to 92.7%) and pH responsiveness and outperform pure alginate capsules, exhibiting contraction and low release rates (<10%) in a simulated stomach environment (pH 1.2) and swelling and sustained release (10 h) in a simulated intestinal environment (pH 7.4). The formation of siloxane bonds between the aminosilane molecules results in stronger and more compact capsule membranes contributing to sustained drug release. Thus, our results demonstrate the potential of the proposed capsules, fabricated using a simple ecofriendly method, as carriers for sustained drug release. [ABSTRACT FROM AUTHOR]

Exosomes are small nanovesicles that are produced through the fusion of multiple veins and plasma membranes, then escaping into adjacent body fluids. Considerable attention has been paid to them due to their potential as delivery vehicles for drugs. Exosomes play a key role in many physiological processes that occur both in healthy and ill states. The production of exosomes depends on the state of the disease, but the disease itself often serves the opposite function by promoting more cell damage and stress. Traditional drug delivery methods often face limitations in terms of specificity, targeted delivery and drug release kinetics. Exosomes have emerged as promising candidates for drug delivery due to their natural ability to selectively deliver cargoes to recipient cells. Exosomes are taken up through various mechanisms, including endocytosis and fusion with target cells. They can encapsulate poorly soluble drugs, enhancing their bioavailability and improving their therapeutic efficacy. Exosomes inspired Lipid Nanovesicles (Exo-LNVs) have shown promising results as drug delivery vehicles. Exosomes have considerable potential as sophisticated vehicle for the delivery of targeted drugs and genes due to their unique characteristics, including inherent stability, minimal immunity and exceptional ability to penetrate tissues and cells. Therapeutic interventions have the capacity to increase effectiveness, reduce side effects and increase patient compliance. Exosomes have the ability to transport various therapeutic by encapsulating different substrates such as nucleic acids, proteins and small molecules. Recent advancements in exosome-inspired lipid nanovesicles have opened up new possibilities for cell-specific drug delivery. These nanovesicles mimic the composition and structure of exosomes, which are naturally occurring extracellular vesicles released by cells. By incorporating therapeutic agents into the lipid nanovesicles, they can effectively target and deliver drugs to specific cells of interest. This review article aims to summarize the current literature on Exo-LNVs and discuss their potential as drug delivery vehicles. A systematic search was conducted to identify relevant studies and relevant data were extracted and analyzed. The review covers various aspects of Exo-LNVs, including their composition, preparation methods and applications in various disease conditions. [ABSTRACT FROM AUTHOR]

Diabetes is a common chronic metabolic disease. Different types of drugs play important roles in controlling diabetes and its complications, but there are some limitations. The glucose-responsive drug delivery system is a novel technology with potential in diabetes treatment. It could automatically release drugs in response to changes in glucose levels in the body to maintain blood glucose within a normal range. The emergence of a glucose-sensitive drug delivery system provides a more intelligent and precise way to treat diabetes. The review is carried out according to the Preferred Reporting Items for Systematic Reviews (PRISMA 2020) guidelines This review focuses on the recent advances in the drugs and different systems of glucose-sensitive drug delivery, including glucose oxidase, phenylboronic acid, Concanavalin A, and other glucose-reactive systems. Furthermore, the glucose-responsive drug delivery system combined with the application applied in hydrogels, microneedles, and nanoparticles is also explored and summarized. The new platforms to sustain the release of anti-diabetic drugs could be desirable for patients. It could lead to increased adherence and glycemic outcomes for the detection and treatment of diabetes. Furthermore, given the limitations of glucose-responsive drug delivery systems, solutions and perspectives are proposed to help the understanding and application of these systems. This review will be helpful for drug discovery and treatment of diabetes from a new perspective. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) poses a risk for numerous metabolic diseases. To date, the U.S. Food and Drug Administration has not yet approved any medications for the treatment of NAFLD, for which developing therapeutic drugs is urgent. Dihydromyricetin (DMY), the most abundant flavonoid in vine tea, has been shown to be hepatoprotective. Its application was limited by low bioavailability in vivo; Methods: In order to improve the bioavailability of DMY and achieve liver-targeted delivery, we designed a DMY-loaded stiff-soft hybrid biomimetic nano drug delivery system (DMY-hNE). The in vivo absorption, distribution, pharmacokinetic profiles, and anti-NAFLD efficacy of DMY-hNE were studied; Results: DMY-hNE was composed of a stiff core and soft shell, which led to enhanced uptake by gastrointestinal epithelial cells and increased penetration of the mucus barrier, thus improving the in vivo absorption, plasma DMY concentration, and liver distribution versus free DMY. In an early NAFLD mouse model, DMY-hNE effectively ameliorated fatty lesions accompanied with reduced lipid levels and liver tissue inflammation; Conclusions: These findings suggested that DMY-hNE is a promising platform for liver drug delivery and treatment of hepatopathy. [ABSTRACT FROM AUTHOR]

Background: This study focused on evaluating the physiochemical characteristics and antibacterial activity of Octoprohibitin-encapsulated CNPs (Octoprohibitin-CNPs) against Acinetobacter baumannii. Methods: Octoprohibitin was encapsulated into CNPs via ionotropic gelation with carboxymethyl chitosan (CMC) and low molecular weight chitosan (CS). Octoprohibitin-CNPs were dispersed in phosphate-buffered saline and the release kinetic profile was determined. Then Octoprohibitin-CNPs were examined using field-emission transmission electron microscopy and physicochemical characterization was performed. Antibacterial activity of Octoprohibitin-CNPs against A. baumannii was evaluated. Biofilm inhibition and eradication assays were performed using the crystal violet (CV) staining-based method for biofilm quantification. Results: The average diameter, zeta potential, encapsulation efficiency, and loading capacity of Octoprohibitin-CNPs were 244.5 ± 21.97 nm, +48.57 ± 0.38 mV, and 85.7% and 34.2%, respectively. TEM analysis imaging revealed that Octoprohibitin-CNPs are irregularly shaped, with fewer aggregates than CNPs. Octoprohibitin-CNPs exhibited a biphasic release pattern, characterized by an initial rapid phase followed by a sustained release over time, extending up to 93.68 ± 6.48% total release until 96 h. In vitro, Octoprohibitin-CNPs showed lower cytotoxicity compared to Octoprohibitin alone. Time-kill kinetic and bacterial viability reduction assays showed Octoprohibitin-CNPs exhibited slightly higher antibacterial activity against A. baumannii than Octoprohibitin. Conclusions: Octoprohibitin-CNP-treated A. baumannii exhibited higher levels of morphological deviation, increased membrane permeability, and the production of reactive oxygen species, as well as antibiofilm activity with greater biofilm inhibition and eradication than Octoprohibitin. These findings show that Octoprohibitin-CNPs perform better against A. baumannii compared to Octoprohibitin alone. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD), characterized by chronic inflammation of the digestive tract, involves angiogenesis as a key pathogenic mechanism. Ginsenoside Rg3, derived from the traditional Chinese herb ginseng, is recognized for its anti-angiogenic properties but is limited by low oral bioavailability. This necessitates the development of an alternative delivery system to improve its therapeutic effectiveness. Methods: Pluronic F-127 (F127) and Pluronic F-68 (F68) were used to construct Rg3-loaded thermosensitive hydrogel Gel-Rg3. Meanwhile, a series of physicochemical properties were determined. Then the safety and pharmacological activity of Gel-Rg3 were evaluated in vitro and in vivo using human umbilical vein endothelial cells (HUVECs) and colitis mouse model, in order to initially validate the potential of Gel-Rg3 for the treatment of IBD. Results: We engineered a rectally administrable, thermosensitive Gel-Rg3 hydrogel using F127 and F68, which forms at body temperature, enhancing Rg3's intestinal retention and slowly releasing the drug. In vitro, Gel-Rg3 demonstrated superior anti-angiogenic activity by inhibiting HUVEC proliferation, migration, and tube formation. It also proved safer and better suited for IBD's delicate intestinal environment than unformulated Rg3. In vivo assessments confirmed increased intestinal adhesion and anti-angiogenic efficacy. Conclusions: The Gel-Rg3 hydrogel shows promise for IBD therapy by effectively inhibiting angiogenesis via rectal delivery, overcoming Rg3's bioavailability limitations with improved safety and efficacy. This study provides new inspiration and data support for the design of treatment strategies for IBD. [ABSTRACT FROM AUTHOR]

The present study synthesized a novel dendrimer with specific functional groups and use them as pharmaceutical carriers at the nanoscale. First, a glycodendrimer was synthesized and a porphyrin substance was selected as its core. Afterward, this substance was subsequently reacted with gallic acid and bromo valerate step-by-step and it was conjugated with acrylonitrile functionalized with Tris (hydroxymethyl) aminomethane. Eventually, the composition was reacted with Tris [α-D Manos (pyrazolyl oxy) methyl] methylamine and glycodendrimer (TTP-Tr-GD) was prepared via a divergent approach to develop drug delivery system. The nanocarrier was characterized using several techniques, such as scanning electron microscopy (FE-SEM), thermal analysis (TGA), NMR, Fourier transform infrared (FT-IR), differential laser scanning (DLS), elemental mapping (EDS), and Zeta potential. Effective factors on the release of the drug delivery, including the best time to absorb, sample pH, and reaction temperature were optimized. The statistically optimized sorption efficiency (98.11%) was attained at pH = 5.5, and a contact time of 15 min. As a result of the functional groups on the surface of the TTP-Tr-GD are appropriate for simultaneous determination and high throughput analysis of drug delivery system. [ABSTRACT FROM AUTHOR]

In order to effectively treat arthritis, this study formulated and evaluated a nanogel containing flurbiprofen and betamethasone. Using ionic gelation technology, nanogels were created by fine-tuning a number of process parameters, such as the concentration of the polymer and cross-linker, as well as the stirring speed, stirring duration, and sonication time. The results demonstrated that the particle size and drug loading efficiency were enhanced as the concentrations of the polymer and cross-linker were increased; the ideal concentrations were 0.4% w/v polymer and 0.4% w/v cross-linker. Particle size was also shown to be greatly affected by stirring duration and speed; particles were found to be smaller while stirring for longer periods of time and faster speeds. Particle size was further reduced to 174.16 nm by sonication for 5 minutes, and the drug loading efficiency was an acceptable 72.02%. The enhanced formulation had a PDI, zeta potential, and particle size distribution that were advantageous, which improved stability and medicine encapsulation. Because it ensures a controlled release of the drug and improves patient outcomes, this nanogel system offers potential as a novel approach to providing anti-inflammatory drugs for the treatment of arthritis. [ABSTRACT FROM AUTHOR]

Fungal infections present significant clinical challenges due to their diverse types and the increasing incidence of drug-resistant strains. Traditional antifungal treatments often encounter issues with penetration, efficacy and patient compliance. The study involves a comprehensive review of the structure and mechanism of transfersomes, their advantages over conventional and other nano carriers, and the integration of herbal extracts. Key aspects include improved skin penetration, enhanced bioavailability of herbal actives, and targeted delivery to infected areas. Transfersomes demonstrate significant benefits in antifungal therapy, including higher efficacy, faster symptom relief, reduced side effects and improved patient compliance. The enhanced penetration and stability of transfersomes facilitate a more effective delivery of herbal actives, making them a superior choice for topical treatments. The study also identifies areas for future research, such as optimizing formulation processes and exploring combination therapies to maximize therapeutic outcomes. Transfersomes represent a transformative advancement in the field of topical drug delivery. Their integration with herbal medicines offers a promising approach to addressing fungal infections more effectively. Future research should focus on clinical validation and further refinement of transfersome-based formulations to fully realize their potential in enhancing the management of fungal infections and other dermatological conditions. [ABSTRACT FROM AUTHOR]

Protein gels prepared by keratin extracted from chicken feathers show potential applications as engineered materials. Feathers are an abundant waste material, whose principal component is keratin, which may have gelling properties not yet sufficiently studied so far which are strongly dependent on the extraction method adopted. The aim of the study is to explore the properties of gels obtained through mercaptoethanol extraction and dialysis process and to evaluate their structural characteristics. The keratin hydrogels were characterized with Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy through which it was possible to identify the secondary structure of the protein on hydrated and dry gel. Moreover, the morphological analysis by scanning electron microscopy (SEM) combined with the rheological analysis showed how the consistency of the gels is maintained on a wide range of loads and frequencies. Furthermore, the biocompatibility of the gels was investigated for the release of subcutaneous drugs using curcumin, an antioxidant polyphenol compound. The fastest release was obtained at pH 7.4, corresponding to physiological conditions. [ABSTRACT FROM AUTHOR]

The purpose of this study was to synthesize and characterize the therapeutic effect of paclitaxel‐loaded polyethylene glycol modified polyethylene imine‐coated iron oxide nanoparticles on cervical cancer cell line (HeLa cell). The physiochemical characteristics of nanocarriers were confirmed by using several methods including X‐ray diffraction (XRD), Thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FT‐IR), Vibrating sample magnetometer (VSM), Dynamic light scattering (DLS), and Transmission electron microscopy (TEM). The results showed the magnetic nanoparticles with size of 35 nm and excellent magnetic properties could load paclitaxel with capacity (16%) and encapsulation efficiency (80%) that has revealed pH‐dependent release behavior. The anticancer effects of nanoparticles were investigated using MTT assay. In comparison to free drug, paclitaxel‐loaded magnetic nanocarrier revealed more cytotoxicity against HeLa cell line and also resulted in an increased rate of apoptotic cancer cells, assessed by flow cytometry analysis. Furthermore, the developed magnetic nanocarrier showed suitable hemocompatibility which can be used in clinical applications. [ABSTRACT FROM AUTHOR]

Capsicum annuum L. var. "Chile de árbol" combined with poly(lactic-co-glycolic acid) (PLGA) and TiO2-ZnO oxides synthesized at different molar ratios and pH (Ti-Zn A and B 3:1, 1:1, and 1:3) via the sol-gel method was characterized by the Brunauer–Emmett–Teller (BET) method, a UV-Vis spectrophotometer (UV-Vis), Fourier transform infrared spectroscopy (FT-IR), High-Performance Liquid Chromatography (HPLC-DAD), and a release profile through mathematical models to explain its behavior. Furthermore, FTIR revealed the presence of PLGA, TiO2, and ZnO as well as amino group characteristics from oleoresin components, principally alkaloid groups (capsaicin and dihydrocapsaicin), as evidenced by HPLC, to identify the presence of capsaicin and dihydrocapsaicin. The UV-Vis spectra showed a slight hypsochromic shift in the PLGA treatments. The release profile demonstrated a higher controllable release in the PLGA treatments than in the double nanoemulsions. Moreover, it is important to note that the effect of NPs influenced the release profile itself, increasing the release when NPs were synthesized at an acidic pH. Therefore, the TiZnOl/PLGA A characteristics suggest that these results have potential for pharmaceutical (as drug carriers) and medical applications. [ABSTRACT FROM AUTHOR]

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Extracellular vesicles (EVs) have been explored as promising drug delivery platforms and cell-free therapies for a range of diseases. Despite their therapeutic potential, challenges persist in achieving sustained EV delivery. Here, we integrate EVs into a supramolecular and injectable hydrogel-based drug delivery system based on dodecyl- or octadecyl-modified hydroxypropyl methylcellulose (HPMC-C12 or -C18) that form non-covalent crosslinks with liposomes. Hydrogel mechanics and EV-release kinetics were tunable by varying liposome concentrations. Using mesenchymal stem cell-derived EVs (MSC-EVs), we confirm effective, hydrogel-mediated sustained EV delivery and uptake and a ~ 20% greater anti-inflammatory response in pathogenic vascular smooth muscle cells than bolus EV-only treatment. [ABSTRACT FROM AUTHOR]

The increasing prominence of biologics in the pharmaceutical market requires more advanced delivery systems to deliver these delicate and complex drug molecules for better therapeutic outcomes. Fibre technology has emerged as a promising approach for creating controlled and targeted drug delivery systems. Fibre-based drug delivery systems offer unprecedented opportunities for improving drug administration, fine-tuning release profiles, and advancing the realm of personalized medicine. These applications range from localized delivery at specific tissue sites to systemic drug administration while safeguarding the stability and integrity of delicate therapeutic compounds. Notwithstanding the promise of fibre-based drug delivery, several challenges such as non-scalability impede cost-effectiveness in the mass production of fibre systems. Biocompatibility and toxicity concerns must also be addressed. Furthermore, issues relating to stability, in-vitro in-vivo correlations, degradation rates, and by-product safety present additional hurdles. Pharmacoinformatics shows the impact of technologies in pharmaceutical processes. Emerging technologies such as Artificial Intelligence (AI) are a transformative force, progressively being applied to enhance various facets of pharmacy, medication development, and clinical healthcare support. However, there is a dearth of studies about the integration of AI in facilitating the translation of predominantly lab-scale pharmaceutical technologies into real-world healthcare interventions. This article explores the application of AI in fibre technology, its potential, challenges, and practical applications within the pharmaceutical field. Through a comprehensive analysis, it presents how the immense capabilities of AI can be leveraged with existing fibre technologies to revolutionize drug delivery and shape the future of therapeutic interventions by enhancing scalability, material integrity, synthesis, and development. [ABSTRACT FROM AUTHOR]

Liver cirrhosis is the end‐stage of chronic liver disease, characterized by inflammation, necrosis, advanced fibrosis, and regenerative nodule formation. Long‐term inflammation can cause continuous damage to liver tissues and hepatocytes, along with increased vascular tone and portal hypertension. Among them, fibrosis is the necessary stage and essential feature of liver cirrhosis, and effective antifibrosis strategies are commonly considered the key to treating liver cirrhosis. Although different therapeutic strategies aimed at reversing or preventing fibrosis have been developed, the effects have not be more satisfactory. In this review, we discussed abnormal changes in the liver microenvironment that contribute to the progression of liver cirrhosis and highlighted the importance of recent therapeutic strategies, including lifestyle improvement, small molecular agents, traditional Chinese medicine, stem cells, extracellular vesicles, and gut remediation, that regulate liver fibrosis and liver cirrhosis. Meanwhile, therapeutic strategies for nanoparticles are discussed, as are their possible underlying broad application and prospects for ameliorating liver cirrhosis. Finally, we also reviewed the major challenges and opportunities of nanomedicine‒biological environment interactions. We hope this review will provide insights into the pathogenesis and molecular mechanisms of liver cirrhosis, thus facilitating new methods, drug discovery, and better treatment of liver cirrhosis. [ABSTRACT FROM AUTHOR]

When skin comes into direct contact with the outside environment, it becomes extremely prone to injury and external factors can make wounds difficult to heal. Traditional medical dressings often cause secondary injury and are poorly resistant to infection. Hydrogels offer a promising alternative to overcome these difficulties. In this study, chitosan (CS)/gelatin (GEL)/polyvinyl alcohol (PVA) hydrogels were developed by chemical cross-linking and loaded with the drug kitasamycin (KM) for testing. The hydrogels' in vitro drug release and wound-healing properties were assessed. For 48 h, the drug release from the hydrogel in vitro persisted, which was significantly longer than the release time of the KM solution. Antimicrobial activity tests showed that the loaded KM hydrogel maintained its bacteriostatic ability at the same concentration as the KM solution, and during in vitro bacteriostatic inhibition, the duration of bacteriostatic inhibition of the KM hydrogel was significantly prolonged compared to that of the KM solution. This confirms the controlled release capability of the hydrogel. In addition, the hydrogel reduced the wound size in mice by 96 % and histopathological tests showed complete re-epithelialization of the wound. The prepared hydrogels successfully demonstrated their potential ability to control drug release and promote skin wound healing. [ABSTRACT FROM AUTHOR]

Copyright of Rare Metals is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The clinical utility of paclitaxel (PTX) is constrained by its poor water solubility and systemic cytotoxicity. Prodrugs of PTX can markedly enhance solubility and reduce the cytotoxicity of the parent drug. However, their efficacy is often constrained by the linkage bond's poor suitable cleavability. In this study, PTX was connected with PEG through a peroxyoxalate linkage bond, a responsive chemical bond of hydrogen peroxide (H2O2). The obtained PTX prodrug polymer (PTX-PEG) can self-assemble into micelles with PTX acting as a hydrophobic core (PTX-PEG/MCs). Notably, the peroxyoxalate linkage bond employed in this study can facilitate the release of the parent drug upon stimulation by reactive oxygen species (ROS), resulting in the generation of carbon dioxide and water as the only byproducts. With the method of solvent evaporation, PTX-PEG/MCs were prepared, and their particle sizes, zeta potentials, appearance morphology, and in vitro stability were characterized. The results show that PTX-PEG/MCs have a particle size of 70.8 ± 1.5 nm and a spherical surface morphology. Also, in an environment of 5 μM H2O2, PTX-PEG can perform responsive cleavages of peroxyoxalate bonds, producing carbon dioxide and water with no effect on the chemical structure of PTX. In vitro experiments show that PTX-PEG/MCs can be efficiently absorbed by tumor cells within 15 min of drug administration, effectively inhibiting the proliferation of 4T1 cells and promoting their apoptosis. In vivo distribution experiments show that fast passive-targeting accumulation of PTX-PEG/MCs can be achieved in mouse tumor tissues. Furthermore, in vivo antitumor experiments demonstrate the potential of PTX-PEG/MCs in inhibiting tumor growth and metastasis and their relatively high biosafety. These research results described above show that PTX-PEG/MCs present the characteristics of H2O2-responsive drug release, which provides a strategy for preparing responsive nanodelivery carriers in a ROS microenvironment of tumors. [ABSTRACT FROM AUTHOR]

Poly(lactic-co-glycolic acid) (PLGA) is a widely used biodegradable and biocompatible copolymer in drug delivery systems (DDSs). In this article, we highlight the critical physicochemical properties of PLGA, including its molecular weight, intrinsic viscosity, monomer ratio, blockiness, and end caps, that significantly influence drug release profiles and degradation times. This review also covers the extensive literature on the application of PLGA in delivering small-molecule drugs, proteins, peptides, antibiotics, and antiviral drugs. Furthermore, we discuss the role of PLGA-based DDSs in the treating various diseases, including cancer, neurological disorders, pain, and inflammation. The incorporation of drugs into PLGA nanoparticles and microspheres has been shown to enhance their therapeutic efficacy, reduce toxicity, and improve patient compliance. Overall, PLGA-based DDSs holds great promise for the advancement of the treatment and management of multiple chronic conditions. [ABSTRACT FROM AUTHOR]

Combination therapies are gaining interest, as they are expected to improve the pharmacological effects. However, current drug combination therapies involve the administration of individual drugs together, which results in differences in delivery efficiency to tumor tissues owing to differences in pharmacokinetics. In the present study, we developed heterodimeric nano-prodrugs (NPDs). We designed a heterodimer of podophyllotoxin and SN-38, from which an NPD with a particle size of approximately 50 nm and a high dispersion stability was fabricated. Our findings contribute to the development of next-generation drug delivery systems capable of co-delivering multiple anticancer agents. [ABSTRACT FROM AUTHOR]

The membrane impermeability of a drug poses a significant challenge in drug research and development, preventing effective drug delivery to the target site. Specifically, the blood-brain barrier (BBB) presents a formidable obstacle to the delivery of drugs targeting the central nervous system (CNS) into the brain, whereas the blood-retinal barrier (BRB) presents a tremendous obstacle to the delivery of drugs targeting the ocular diseases into the eyes. The development of drugs for Alzheimer's or Parkinson's disease targeting the CNS and for diabetic retinopathy and age-related macular degeneration targeting the eyes remains an unmet medical need for patients. Transporters play a crucial physiological role in maintaining homeostasis in metabolic organs. Various types of solute carrier (SLC) transporters are expressed in the capillary endothelial cells of the BBB, facilitating the delivery of nutrients from the blood flow to the brain. Therefore, carrier-mediated transport across the BBB can be achieved using SLC transporters present in capillary endothelial cells. It is well-known that CNS drugs typically incorporate N-containing groups, indicating that cation transporters facilitate their transport into the brain. In fact, carrier-mediated transport across the BBB can be accomplished using glucose transporter type 1 (Glut1) as a glucose transporter, L-type amino acid transporter 1 (LAT1) as a large neutral amino acid transporter, and H+/cation antiporter as a cation transporter. Surprisingly, although organic cation transporter novel type 2 (OCTN2) is expressed in the capillary endothelial cells, there has been limited investigation into OCTN2-mediated substance delivery into the brain across the BBB. Furthermore, it is suggested that OCTN2 is expressed at the BRB. In this prospective review, I present the advantages and possibilities of substance delivery into the brain across the BBB or into the eyes across the BRB, mediated by OCTN2 via carrier-mediated transport or receptor-mediated transcytosis. [ABSTRACT FROM AUTHOR]

Although various chemically synthesized materials are essential in medicine, food, and agriculture, they can exert unexpected side effects on the environment and human health by releasing certain toxic chemicals. Therefore, eco-friendly and biocompatible biomaterials based on natural resources are being actively explored. Recently, biosilica derived from diatoms has attracted attention in various biomedical fields, including drug delivery systems (DDS), due to its uniform porous nano-pattern, hierarchical structure, and abundant silanol functional groups. Importantly, the structural characteristics of diatom biosilica improve the solubility of poorly soluble substances and enable sustained release of loaded drugs. Additionally, diatom biosilica predominantly comprises SiO2, has high biocompatibility, and can easily hybridize with other DDS platforms, including hydrogels and cationic DDS, owing to its strong negative charge and abundant silanol groups. This review explores the potential applications of various diatom biosilica-based DDS in various biomedical fields, with a particular focus on hybrid DDS utilizing them. [ABSTRACT FROM AUTHOR]

Since drug release behavior depends on the interaction between the drugs and carriers, the present work is to study the drug delivery system based on magnesium aluminum layered double hydroxides containing europium (MgAl-Eu-LDH) for chlorogenic acid (CGA). Various characterizations, including X-ray diffraction (XRD), infrared spectrum, zeta potentials, UV–Vis absorption spectrum, scanning electron scanning electron microscope equipped with energy-dispersive X-ray spectroscopy (SEM–EDS), CHN elemental analysis, and fluorescent spectra, were employed to investigate the drug delivery system. Results revealed that the CGA was loaded into MgAl-Eu-LDH. The drug delivery system based on MgAl-Eu-LDH exhibited more slow and sustained release of CGA compared with that of the previous methotrexate or 5-fluorouracil, and the drug release experiment can be reproducible. Moreover, the MgAl-Eu-LDH showed different fluorescence before loading CGA, during loading CGA, and after releasing CGA. These results may provide a reference for the development of CGA drug delivery systems with slow and sustained release. [ABSTRACT FROM AUTHOR]

Drug resistance remains a critical barrier in cancer therapy, diminishing the effectiveness of chemotherapeutic, targeted, and immunotherapeutic agents. Overexpression of proteins such as B-cell lymphoma 2 (Bcl-2), inhibitor of apoptosis proteins (IAPs), protein kinase B (Akt), and P-glycoprotein (P-gp) in various cancers leads to resistance by inhibiting apoptosis, enhancing cell survival, and expelling drugs. Although several inhibitors targeting these proteins have been developed, their clinical use is often hampered by systemic toxicity, poor bioavailability, and resistance development. Nanoparticle-based drug delivery systems present a promising solution by improving drug solubility, stability, and targeted delivery. These systems leverage the Enhanced Permeation and Retention (EPR) effect to accumulate in tumor tissues, reducing off-target toxicity and increasing therapeutic efficacy. Co-encapsulation strategies involving anticancer drugs and resistance inhibitors within nanoparticles have shown potential in achieving coordinated pharmacokinetic and pharmacodynamic profiles. This review discusses the mechanisms of drug resistance, the limitations of current inhibitors, and the advantages of nanoparticle delivery systems in overcoming these challenges. By advancing these technologies, we can enhance treatment outcomes and move towards more effective cancer therapies. [ABSTRACT FROM AUTHOR]

A targeted micellar formation of doxorubicin (Dox) and curcumin (Cur) was evaluated to enhance the efficacy and reduce the toxicity of these drugs in KG1a leukemic stem cells (LSCs) compared to EoL-1 leukemic cells. Dox-Cur-micelle (DCM) was developed to improve the cell uptake of both compounds in LSCs. Cur-micelle (CM) was produced to compare with DCM. DCM and CM were conjugated with two FLT3 (FMS-like tyrosine kinase)-specific peptides (CKR; C and EVQ; E) to increase drug delivery to KG1a via the FLT3 receptor (AML marker). They were formulated using a film-hydration technique together with a pH-induced self-assembly method. The optimal drug-to-polymer weight ratios for the DCM and CM formulations were 1:40. The weight ratio of Dox and Cur in DCM was 1:9. DCM and CM exhibited a particle size of 20–25 nm with neutral charge and a high %EE. Each micelle exhibited colloidal stability and prolonged drug release. Poloxamer 407 (P407) was modified with terminal azides and conjugated to FLT3-targeting peptides with terminal alkynes. DCM and CM coupled with peptides C, E, and C + E exhibited a higher particle size. Moreover, DCM-C + E and CM-C + E showed the highest toxicity in KG-1a and EoL-1 cells. Using two peptides likely improves the probability of micelles binding to the FLT3 receptor and induces cytotoxicity in leukemic stem cells. [ABSTRACT FROM AUTHOR]

Over decades of development, the modern drug delivery system continues to grapple with numerous challenges, including drug loading inefficiencies, issues of immunogenicity, and cytotoxicity. These limitations restrict its application across various systems. Microalgae, as a natural resource, are not only abundant in bioactive compounds but also possess multiple biological properties, including active surface, photosynthesis capabilities, and excellent biocompatibility. These attributes make microalgae highly promising as carriers for targeted drug delivery, offering significant potential for the diagnosis and treatment of various diseases. Therefore, leveraging the exceptional properties of microalgae for drug delivery and optimizing their qualities is of paramount importance. This article focuses on elucidating the biological characteristics of microalgae and their applications in drug delivery, with a particular emphasis on emerging strategies for efficient drug loading and precise targeted delivery. Microalgae, as a natural biomaterial, hold immense potential for both commercial and clinical applications. [ABSTRACT FROM AUTHOR]

Malignant melanoma (MM) is an extremely aggressive and fatal form of skin cancer that primarily affects the bottom layer of the epidermis and is associated with poor clinical outcomes. Early-stage MM is typically treated through surgical removal, while chemotherapy and radiotherapy are common conventional treatment options that come with harmful side effects. Emerging therapies such as immunotherapy, photodynamic therapy, biologic therapy, and photothermal therapy present hopeful options for treatment due to their effective and secure drug delivery methods. To address the limitations of current treatment options, advanced methods of drug delivery for subcutaneous MM are being developed, with hydrogels emerging as a promising alternative. To date, significant advancements have been made in the treatment of MM through the use of hydrogels-based drug delivery systems through focal plastering, injection, implantation, and microneedles. Recent research on hydrogel-based drug delivery systems that integrate multiple therapies for the treatment of subcutaneous MM is discussed in this review. [ABSTRACT FROM AUTHOR]

C. neoformans , a life-threatening invasive fungal pathogen, can hijack the pulmonary macrophages as 'Trojan horse', leading to cryptococcal meningitis and recurrence. Combatting these elusive fungi has posed a long-standing challenge. Here, we report an inhaled cascade-targeting drug delivery platform that can sequentially target host cells and intracellular fungi. The delivery system involves encapsulating amphotericin B (AMB) into polymeric particles decorated with AMB, creating a unique surface pattern, denoted as APP@AMB. The surface topology of APP@AMB guides the efficient macrophages internalization and intracellular drugs accumulation. Following endocytosis, the surface-functionalized AMB specifically targets intracellular fungi by binding to ergosterol in the fungal membrane, as demonstrated through co-localization studies using confocal microscopy. Through on-site AMB delivery, APP@AMB displays superior efficacy in eliminating C. neoformans in the lungs and brain compared to free AMB following inhalation in infected mice. Additionally, APP@AMB significantly alleviates the nephrotoxicity associated with free AMB inhalation therapy. Thus, this biocompatible delivery system enabling host cells and intracellular fungi targeting in a cascade manner, provides a new avenue for the therapy of fungal infection. [Display omitted] • This study developed inhaled polymer particles for the delivery of Amphotericin B in the treatment of fungal infections. • The unique topology and ligand facilitate targeted delivery of AMB for treating cryptococcus intracellular infections. • The results demonstrate the potential for eradicating intracellular fungi through cascade-targeting delivery of AMB. [ABSTRACT FROM AUTHOR]

Immunogenic cell death (ICD) holds the potential for in situ tumor vaccination while concurrently eradicating tumors and stimulating adaptive immunity. Most ICD inducers, however, elicit insufficient immune responses due to negative feedback against ICD biomarkers, limited infiltration of antitumoral immune cells, and the immunosuppressive tumor micro-environment (TME). Recent findings highlight the pivotal roles of stimulators of interferon gene (STING) activation, particularly in stimulating antigen-presenting cells (APCs) and TME reprogramming, addressing ICD limitations. Herein, we introduced 'tumor phagocytosis-driven STING activation', which involves the activation of STING in APCs during the recognition of ICD-induced cancer cells. We developed a polypeptide-based nanocarrier encapsulating both doxorubicin (DOX) and diABZI STING agonist 3 (dSA3) to facilitate this hypothesis in vitro and in vivo. After systemic administration, nanoparticles predominantly accumulated in tumor tissue and significantly enhanced anticancer efficacy by activating tumor phagocytosis-driven STING activation in MC38 and TC1 tumor models. Immunological activation of APCs occurred within 12 h, subsequently leading to the activation of T cells within 7 days, observed in both the TME and spleen. Furthermore, surface modification of nanoparticles with cyclic RGD (cRGD) moieties, which actively target integrin α v β 3 , enhances tumor accumulation and eradication, thereby verifying the establishment of systemic immune memory. Collectively, this study proposes the concept of tumor phagocytosis-driven STING activation and its effectiveness in generating short-term and long-term immune responses. [Display omitted] [ABSTRACT FROM AUTHOR]

This research investigated the in vivo gelation, biodegradation, and drug release efficiency of a novel injectable sensitive drug delivery system for human growth hormone (HGh). This composite system comprises pH- and temperature-sensitive hydrogel, designated as oligomer serine-b-poly(lactide)-b-poly(ethylene glycol)-b-poly(lactide)-b-oligomer serine (OS-PLA-PEG-PLA-OS) pentablock copolymer, as matrix and electrosprayed HGh-loaded chitosan (HGh@CS) nanoparticles (NPs) as principal material. The proton nuclear magnetic resonance spectrum of the pH- and temperature-sensitive OS-PLA-PEG-PLA-OS pentablock copolymer hydrogel proved that this copolymer was successfully synthesized. The HGh was encapsulated in chitosan (CS) NPs by an electrospraying system in acetic acid with appropriate granulation parameters. The scanning electron microscopy images and size distribution showed that the HGh@CS NPs formed had an average diameter of 366.1 ± 214.5 nm with a discrete spherical shape and dispersed morphology. The sol–gel transition of complex gel based on HGh@CS NPs and OS-PLA-PEG-PLA-OS pentablock hydrogel was investigated at 15 °C and pH 7.8 in the sol state and gelled at 37 °C and pH 7.4, which is suitable for the physiological conditions of the human body. The HGh release experiment of the composite system was performed in an in vivo environment, which demonstrated the ability to release HGh, and underwent biodegradation within 32 days. The findings of the investigation revealed that the distribution of HGh@CS NPs into the hydrogel matrix not only improved the mechanical properties of the gel matrix but also controlled the drug release kinetics into the systematic bloodstream, which ultimately promotes the desired therapeutic body growth depending on the distinct concentration used. [ABSTRACT FROM AUTHOR]

Chondroitin sulfate (CS) is a linear polysaccharide chain of alternating residues of glucuronic acid (GlcA) and N -acetylgalactosamine (GalNAc), modified with sulfate groups. Based on the structure, CS chains bind to bioactive molecules specifically and regulate their functions. For example, CS whose GalNAc is sulfated at the C4 position, termed CSA, and CS whose GalNAc is sulfated at both C4 and C6 positions, termed CSE, bind to a malaria protein VAR2CSA and receptor type of protein tyrosine phosphatase sigma (RPTPσ), respectively, in a specific manner. Here, we modified CSA and CSE chains with phosphatidylethanolamine (PE) at a reducing end, attached them to liposomes containing phospholipids and generated CSA and CSE liposomes. The CS-PE was incorporated into the liposome particles efficiently. Inhibition ELISA revealed specific interaction of CSA and CSE with recombinant VAR2CSA and RPTPσ, respectively, more efficiently than CS chains alone. Furthermore, CSE liposome was specifically incorporated into RPTPσ-expressing HEK293T cells. These results indicate CS liposome as a novel and efficient drug delivery system, especially for CS-binding molecules. [ABSTRACT FROM AUTHOR]

To evaluate the safety and intraocular pressure (IOP)-lowering efficacy of 2 models of the travoprost intraocular implant (fast-eluting [FE] and slow-eluting [SE] types) from 1 of 2 phase 3 trials (the GC-010 trial). Multicenter, randomized, double-masked, sham-controlled, noninferiority trial. Patients with open-angle glaucoma or ocular hypertension having an unmedicated baseline mean diurnal IOP (average of 8 am , 10 am , and 4 pm time points) of ≥ 21 mmHg, and IOP of ≤ 36 mmHg at each of the 8 am , 10 am , and 4 pm timepoints at baseline. Study eyes were randomized to the travoprost intraocular implant (FE implant [n = 200] or SE implant [n = 197] model) or to timolol ophthalmic solution 0.5% twice daily (n = 193). The primary outcome was mean change from baseline IOP in the study eye at 8 am and 10 am , at each of day 10, week 6, and month 3. Safety outcomes included adverse events (AEs) and ophthalmic assessments. Mean IOP reduction from baseline over the 6 time points ranged from 6.6 to 8.4 mmHg for the FE implant group, from 6.6 to 8.5 mmHg for the SE implant group, and from 6.5 to 7.7 mmHg for the timolol group. The primary efficacy end point was met; the upper limit of the 95% confidence interval of the difference between the implant groups and the timolol group was < 1 mmHg at all 6 time points. Study eye AEs, most of mild or moderate severity, were reported in 21.5%, 27.2%, and 10.8% of patients in the FE implant, SE implant, and timolol groups, respectively. The most common AEs included iritis (FE implant, 0.5%; SE implant, 5.1%), ocular hyperemia (FE implant, 3.0%; SE implant, 2.6%), reduced visual acuity (FE implant, 1.0%; SE implant, 4.1%; timolol, 0.5%), and IOP increased (FE implant, 3.5%; SE implant, 2.6%; timolol, 2.1%). One serious study eye AE occurred (endophthalmitis). The travoprost intraocular implant demonstrated robust IOP reduction over the 3-month primary efficacy evaluation period after a single administration. The IOP-lowering efficacy in both implant groups was statistically and clinically noninferior to that in the timolol group, with a favorable safety profile. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

Oxidative stress is implicated in the pathophysiology of several illnesses. Catalase (CAT), an antioxidant enzyme, remains a prime target for oxidative stress related therapies. Unfortunately, the labile nature, difficulty in recovering and reusing, and insufficient delivery systems limit its use in therapy. This study used a simple biomineralization process for the synthesis of vaterite porous calcium carbonate (CaCO 3) microspheres (MS) for the development of cross-linked immobilized (CAT-MS). Scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), particle size analysis, and zeta-potential measurements were used for CaCO 3 -MS characterization. CAT was immobilized efficiently with a high immobilization yield (99 %). The immobilized enzyme had a higher Km than free CAT with a 1.7 fold increase in Vmax and Kcat. CAT-MS displayed a longer half-life, efficient reusability, enhanced storage stability, and excellent stability against various denaturants compared to free CAT. Furthermore, CAT-MS demonstrated negligible cytotoxicity in the fibroblast cell line (BJ1), where CAT-MS recorded higher cell viability than free CAT, (p< 0.05) indicating exceptional biocompatibility. This study raises the potential of an eco-friendly approach that enforces wide and safe catalase application in intracellular therapy for treating oxidative stress-associated diseases. [Display omitted] • Catalase-loaded CaCO 3 microspheres (CAT-MS) were synthesized by a modified process. • High immobilization yield and prominent loading efficiency were achieved. • CAT-MS had a longer half-life and enhanced thermal and storage stability. • immobilization improved reusability and stability against various denaturants. • CAT-MS demonstrated high biocompatibility in vitro cell line. [ABSTRACT FROM AUTHOR]

Introduction: This study was conducted to analyze and compare the intraocular pressure (IOP) treatment effect of the slow-eluting (SE) travoprost intracameral implant to the IOP treatment effect of topical prostaglandin analog (PGA) monotherapy in a subgroup of subjects who were on pre-study PGA monotherapy prior to enrollment in the two pivotal phase 3 trials of the travoprost intracameral implant. Methods: A combined study population of 133 subjects from two phase 3 trials, who were on topical PGA monotherapy at screening, subsequently underwent a washout period from their topical PGA, and then were randomized and administered an SE travoprost intracameral implant. The subjects were analyzed for the IOP treatment effects of the pre-study topical PGA monotherapy and the in-study SE travoprost intracameral implant. Paired t-tests were used to compare the difference in screening minus post-washout baseline IOP versus month 3 minus post-washout baseline IOP. The IOP-lowering efficacy in eyes administered an SE travoprost intracameral implant was compared to the IOP lowering in the same eyes while on a topical PGA monotherapy prior to study entry. Results: Pre-study topical PGA monotherapy and the SE travoprost intracameral implant demonstrated IOP treatment effects of −5.76 mmHg and −7.07 mmHg, respectively. The IOP-lowering treatment effect was significantly greater by 1.31 mmHg for the SE travoprost intracameral implant relative to pre-study PGA monotherapy (95% confidence interval: −2.01, −0.60; P = 0.0003). Conclusions: The SE travoprost intracameral implant demonstrated superior IOP-lowering treatment effect versus pre-study topical PGA monotherapy with a superiority margin that was both statistically significant and clinically meaningful. The greater IOP reduction from baseline while on the SE implant versus pre-study topical PGA monotherapy may be a reflection of the optimized adherence and continuous elution of PGA therapy into the anterior chamber achieved with the SE travoprost intracameral implant. Trial Registration: ClinicalTrials.gov identifiers, NCT03519386 and NCT03868124. [ABSTRACT FROM AUTHOR]

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Quercetin (QC) is a matchable option for cancer remedy, lessens the issues relevant to low solvability, and its quick release has become urgent. This research used a newfound nanocarrier based on a hydrogel nanocomposite, including polyvinylpyrrolidone (PVP), agarose (Aga), and ZIF-8 nanoparticles to load QC. Being of nanocomposite ingredients was authenticated by FTIR and XRD analysis. The surface correlation of the nanocomposite and stability of the nanocarrier produced was approved by FESEM images, Zeta, and DLS analysis, consecutively. With ZIF-8, drug loading is 47.50%, and encapsulation is 86.75%. Prolonged pH-sensitive release lasted about 100 h. Based on the R2 amounts of the models employed to correspond to the drug release data, the Higuchi model can well explain release data at pH 5.4. The reduction in a living MCF-7 cell in the presence of PVP/Aga/ZIF-8 samples compared to PVP/Aga samples and the control sample portends the ZIF-8 in vitro cytotoxicity. The percent of late apoptotic cells in PVP/Aga/ZIF-8@QC (14.0%) is higher than in other samples (Control, PVP/Aga/ZIF-8), which may be owing to the controlled and slow release of QC from PVP/Aga/ZIF-8@QC. [ABSTRACT FROM AUTHOR]

We aimed to perform a comprehensive study on the development and characterization of silymarin (Syl)-loaded niosomes as potential drug delivery systems. The results demonstrate significant novelty and promising outcomes in terms of morphology, size distribution, encapsulation efficiency, in vitro release behavior, free energy profiles of Syl across the niosome bilayer, hydrogen bonding interactions, antimicrobial properties, cytotoxicity, and in vivo evaluations. The physical appearance, size, and morphology assessment of free niosomes and Syl-loaded niosomes indicated stable and well-formed vesicular structures suitable for drug delivery. Transmission electron microscopy (TEM) analysis revealed spherical shapes with distinct sizes for each formulation, confirming uniform distribution. Dynamic light scattering (DLS) analysis confirmed the size distribution results with higher polydispersity index for Syl-loaded niosomes. The encapsulation efficiency of Syl in the niosomes was remarkable at approximately 91%, ensuring protection and controlled release of the drug. In vitro release studies showed a sustained release profile for Syl-loaded niosomes, enhancing therapeutic efficacy over time. Free energy profiles analysis identified energy barriers hindering Syl permeation through the niosome bilayer, emphasizing challenges in drug delivery system design. Hydrogen bonding interactions between Syl and niosome components contributed to energy barriers, impacting drug permeability. Antimicrobial assessments revealed significant differences in inhibitory effects against S. aureus and E. coli. Cytotoxicity evaluations demonstrated the superior tumor-killing potential of Syl-loaded niosomes compared to free Syl. In vivo studies indicated niosome formulations' safety profiles in terms of liver and kidney parameters compared to bulk Syl, showcasing potential for clinical applications. Overall, this research highlights the promising potential of Syl-loaded niosomes as effective drug delivery systems with enhanced stability, controlled release, and improved therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Abstract Cardiovascular diseases have been the leading cause of global mortality and disability. In addition to traditional drug and surgical treatment, more and more studies investigate tissue engineering therapeutic strategies in cardiovascular medicine. Collagen interweaves in the form of trimeric chains to form the physiological network framework of the extracellular matrix of cardiac and vascular cells, possessing excellent biological properties (such as low immunogenicity and good biocompatibility) and adjustable mechanical properties, which renders it a vital tissue engineering biomaterial for the treatment of cardiovascular diseases. In recent years, promising advances have been made in the application of collagen materials in blood vessel prostheses, injectable cardiac hydrogels, cardiac patches, and hemostatic materials, although their clinical translation still faces some obstacles. Thus, we reviewed these findings and systematically summarizes the application progress as well as problems of clinical translation of collagen biomaterials in the cardiovascular field. The present review contributes to a comprehensive understanding of the application of collagen biomaterials in cardiovascular medicine. Graphical abstract

Xiaozhu Zha,1,&ast; Yumei Hao,2,&ast; Yifan Ke,1 Yichun Wang,3 Yujia Zhang2 1Department of Traditional Chinese Medicine, Anqing Medical College, Anqing, People’s Republic of China; 2Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, People’s Republic of China; 3Department of Radiation Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yichun Wang; Yujia Zhang, Email wangechun321@sina.com; zhyj@imm.ac.cnBackground: Liver fibrosis is a necessary pathological process in many chronic liver diseases. Studies have shown that the progression of chronic liver disease can be slowed by rational intervention in hepatic fibrosis. Berberine (BBR), a natural extract of Phellodendron amurense, inhibits the development of liver fibrosis through several mechanisms. However, the clinical application of BBR is limited due to its low solubility. Drug delivery systems have been developed to improve the solubility of hydrophobic drugs and increase their efficacy in treating the liver fibrosis.Methods: In this study, a biocompatible nanomicelle was constructed by thin-film dispersion method using polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PVCL-PVA-PEG) as a carrier to encapsulate BBR (PVCL-PVA-PEG/BBR-MCs) to improve the solubility of BBR and reduce the systemic side effects. The ability to inhibit HSC-T6 cell activation of PVCL-PVA-PEG/BBR-MCs was evaluated in vitro. The anti-hepatic fibrosis effects of PVCL-PVA-PEG/BBR-MCs were investigated in vivo.Results: PVCL-PVA-PEG/BBR-MCs have a uniform spherical shape with a mean particle size of 60.04 ± 0.027 nm and a potential of 1.49 ± 0.32 mV. It had an encapsulation efficiency of 98.52% ± 0.70 and drug loading content of 6.16% ± 0.04. Compared to free BBR, PVCL-PVA-PEG/BBR-MCs significantly inhibited HSC-T6 cell activation and TGF-β 1-induced HSC-T6 cell migration in vitro. In vivo biodistribution experiments showed significantly improved hepatic distribution of PVCL-PVA-PEG/DiD-MCs compared to free DiD, suggesting that PVCL-PVA-PEG micelles enhance the ability of BBR to enter the liver and improve therapeutic efficacy. After treatment, PVCL-PVA-PEG/BBR-MCs significantly improved fibrotic liver structure and reduced collagen deposition in comparison to the CCl4-treated group; the treatment outcome was more effective than that of the free BBR group.Conclusion: Our results demonstrate the advantages of encapsulating BBR in PVCL-PVA-PEG micelles and highlight the potential of PVCL-PVA-PEG/BBR-MCs as a therapeutic strategy for the treatment of liver fibrosis. Keywords: liver fibrosis, berberine, hepatic stellate cells, PVCL-PVA-PEG, drug delivery system

Chika Akinseye,1 Andrew Fiorini,2 Emily Louise Jarvis,3 Michelle Fry,4 Abid Raza,5 Sara Soleman,6 Stephanie Igwe,6 Mark Palmer2 1GSK R&D, Discovery Medicine, Stevenage, UK; 2GSK R&D, Device Engineering, Ware, UK; 3GSK R&D, Biostatistics, Stevenage, UK; 4GSK Rx Global Clinical Delivery, Stockley Park, UK; 5GSK R&D, Stockley Park, UK; 6GSK Clinical Unit, Addenbrooke’s Centre for Clinical Investigation, Cambridge, UKCorrespondence: Mark Palmer, GSK R&D, Harris’s Lane Ware, Hertfordshire, SG12 0DP, United Kingdom, Email mark.g.palmer@gsk.comPurpose: Therapeutic proteins are often delivered by subcutaneous (SC) autoinjector to enable self-administration. Autoinjectors typically deliver up to 1 mL injected volumes per dose. Delivery of larger volumes may be limited by injection site discomfort, including pain, swelling, and redness. Delivery at a slower rate may mitigate this discomfort. This single-center, randomized, crossover study evaluated the acceptability and tolerability of varying volumes and delivery rates of SC saline in healthy volunteers.Patients and Methods: Eligible participants were adults (18– 65 years) with a body mass index of 18.5– 32.0 kg/m2. Participants (N = 24) were randomized to multiple sequences of infusions over five visits, with infusions ranging from 1 to 5 mL at rates of 1.50– 6.00 mL/minute (min) and including a 1 mL SC infusion in 10 seconds (s) at a rate of 6.00 mL/min. The primary objective was to identify acceptable volume and delivery rates of SC saline, as assessed by visual analogue scale (VAS) pain scores, a tolerability and acceptability questionnaire, and infusion leakage.Results: Infusions that met the acceptability criteria were 1 mL in 10s, 4 mL in 58s, and 3 mL in 2 mins. Higher delivery volumes and rates were associated with higher VAS pain scores but remained within the VAS acceptability criteria.Conclusion: These findings may support the development of larger-volume injectors for self-administration of future medicines.Keywords: drug delivery system, skin, formulation, pain scores, tolerability and acceptability questionnaire

Shouye Sun,1 Qian Wang,2 Bin Zhang,3 Yutao Cui,1 Xinghui Si,4 Gan Wang,1 Jingwei Wang,1 Hang Xu,1 Baoming Yuan,1 Chuangang Peng1 1Orthopaedic Medical Center, The Second Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Otolaryngology, The First Hospital of Jilin University, Changchun, People’s Republic of China; 3Department of Spinal Surgery, The 964th Hospital of PLA Joint Logistic Support Force, Changchun, People’s Republic of China; 4Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, People’s Republic of ChinaCorrespondence: Baoming Yuan, Orthopaedic Medical Center, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of China, Email yuanbm@jlu.edu.cnPurpose: During treatment of infected bone defects, control of infection is necessary for effective bone repair, and hence controlled topical application of antibiotics is required in clinical practice. In this study, a biodegradable drug delivery system with in situ gelation at the site of infection was prepared by integrating vancomycin into a polyethylene glycol/oxidized dextran (PEG/ODEX) hydrogel matrix.Methods: In this work, PEG/ODEX hydrogels were prepared by Schiff base reaction, and vancomycin was loaded into them to construct a drug delivery system with controllable release and degradability. We first examined the microstructure, degradation time and drug release of the hydrogels. Then we verified the biocompatibility and in vitro ability of the release system. Finally, we used a rat infected bone defect model for further experiments.Results: The results showed that this antibacterial system could be completely biodegradable in vivo for 56 days, and its degradation products did not cause specific inflammatory response. The cumulative release of vancomycin from the antibacterial system was 58.3% ± 3.8% at 14 days and 78.4% ± 3.2% at 35 days. The concentration of vancomycin in the surrounding environment was about 1.2 mg/mL, which can effectively remove bacteria. Further studies in vivo showed that the antibacterial system cleared the infection and accelerated repair of infected bone defects in the femur of rats. There was no infection in rats after 8 weeks of treatment. The 3D image analysis of the experimental group showed that the bone volume fraction (BV/TV) was 1.39-fold higher (p < 0.001), the trabecular number (Tb.N) was 1.31-fold higher (p < 0.05), and the trabecular separation (Tb.Sp) was 0.58-fold higher than those of the control group (p < 0.01).Conclusion: In summary, this study clearly demonstrates that a clinical strategy based on biological materials can provide an innovative and effective approach to treatment of infected bone defects.Keywords: infected bone defects, drug delivery system, hydrogel, vancomycin

Dapsone (DAP) is used to treat leprosy, a Neglected tropical diseases (NTDs). However, its low solubility often leads to low efficacy. In this work, ZIF-8 nanostructures loaded with DAP (DAP@ZIF-8) were successfully synthesized with suitable drug loading (DL) through a one-pot synthesis. Different parameters of the synthesis method were evaluated in terms of DL and crystal structure, and the optimized systems were characterized regarding crystallinity, morphology, molecular interactions, hydrodynamic size, and thermal stability. The results showed that the water/DMSO synthesis was effective in entrapping DAP (11.1%±2.8), providing characteristic morphology and crystal structure of ZIF-8. Particle size (193.4 ± 1.1 and 168.7 ± 2.0), polydispersity index (≤ 0.2), and zeta potential (11.4 ± 5.1 and 19.6 ± 3.13) results were consistent with nanostructured systems for both ZIF-8 and DAP@ZIF-8, respectively. Electron micrographs demonstrated the nanosized structures and their shapes, and FT-IR spectra confirmed the encapsulation of DAP and its intermolecular interactions with the organic fraction of ZIF-8. Thermal analysis confirmed the degradation profile of ZIF-8 and the molecular dispersion of DAP. In summary, the one-pot synthesis of DAP@ZIF-8 has been successfully employed to obtain an innovative system capable of loading over 10% drug, which significantly improves over other nano-based systems and represents a promising DAP delivery platform. [ABSTRACT FROM AUTHOR]

Recent research is based on biocompatible drug delivery systems due to the need for bioavailability, route of administration, dose dumping, and first-pass metabolism. Despite its excellent mechanical strength, elasticity, and stability, polyurethane has associated risk factors such as high hydrophobic nature and long-term degradability. This review focuses on providing insight into polyurethane as a drug delivery system. The key objective of the review is to signify the importance of polyurethane in biomedical, the essential compounds to synthesize polyurethane, and the types of polyurethane. The review has highlighted polyurethane's drug loading and release capacity and its composites in various forms. The essential biological studies such as polyurethane's antibacterial, antiinflammatory, and anticancer activity were also discussed. Herein, polyurethane and its hybrid composites can be a potential material for future implantable drug delivery systems. [ABSTRACT FROM AUTHOR]