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The combination of paclitaxel (PTX) with other chemotherapy drugs (e.g., gemcitabine, GEM) or genetic drugs (e.g., siRNA) has been shown to enhance therapeutic efficacy against tumors, reduce individual drug dosages, and prevent drug resistance associated with single-drug treatments. However, the varying solubility of chemotherapy drugs and genetic drugs presents a challenge in co-delivering these agents. In this study, nanoparticles loaded with PTX were prepared using the biodegradable polymer material poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx). These nanoparticles were surface-modified with target proteins (Affibody molecules) and RALA cationic peptides to create core-shell structured microspheres with targeted and cationic functionalization. A three-drug co-delivery system (PTX@PHBHHx-ARP/siRNAGEM) were developed by electrostatically adsorbing siRNA chains containing GEM onto the microsphere surface. The encapsulation efficiency of PTX in the nanodrug was found to be 81.02%, with a drug loading of 5.09%. The chemogene adsorption capacity of siRNAGEM was determined to be 97.3%. Morphological and size characterization of the nanodrug revealed that PTX@PHBHHx-ARP/siRNAGEM is a rough-surfaced microsphere with a particle size of approximately 150 nm. This nanodrug exhibited targeting capabilities toward BT474 cells with HER2 overexpression while showing limited targeting ability toward MCF-7 cells with low HER2 expression. Results from the MTT assay demonstrated that PTX@PHBHHx-ARP/siRNAGEM exhibits high cytotoxicity and excellent combination therapy efficacy compared to physically mixed PTX/GEM/siRNA. Additionally, Western blot analysis confirmed that siRNA-mediated reduction of Bcl-2 expression significantly enhanced cell apoptosis mediated by PTX or GEM in tumor cells, thereby increasing cell sensitivity to PTX and GEM. This study presents a novel targeted nanosystem for the co-delivery of chemotherapy drugs and genetic drugs. [ABSTRACT FROM AUTHOR]

Background: It is well known that periodontitis affects the gums and surrounding connective tissue. The chronic inflammatory response induced by bacteria in the gingival tissue leads to the loss of the collagen connection between the tooth and the bone and ultimately to bone loss. Methods: In this context, the aim of this research was the obtaining and characterization of a drug release supports in the form of sponges based on collagen, hyaluronic acid as a support and metronidazole as an antibiotic for the treatment of periodontitis. The sponges were characterized by FT-IR spectroscopy, water uptake, contact angle, SEM microscopy, in vitro metronidazole release analysis from sponges and data modeling. Results: The results showed that all the sponges had a porous structure with interconnected pores, the pore sizes being influenced by hyaluronic acid and metronidazole; the spongious structure became much more dense for samples with metronidazole content. All metronidazole-loaded sponges showed good surface wettability and an adequate swelling capacity for a suitable antimicrobial release at the periodontal pocket. The porous structures allow a controlled release, fast in the first hour, essential to control the initial microbial load at the periodontal level, which continues slowly in the following hours to ensure an effective treatment of periodontitis. Conclusions: Correlating all physical–chemical and bio-pharmaceutical results obtained, a promising solution for periodontitis treatment could be a met-ronidazole–collagen–hyaluronic system consisting of 1% collagen, 1.5% metronidazole and 0.8% hyaluronic acid, and in vitro and in vivo tests are recommended to continue studies. [ABSTRACT FROM AUTHOR]

In addition to the solubilization of poorly water-soluble, highly lipophilic drugs, lipid nanoemulsions bear potential for drug targeting approaches. This requires that the drug remains within the emulsion droplets until they reach the site of action. Since drug release is rather controlled by the lipophilicity of the drug than by the formulation, this study systematically investigated the influence of drug lipophilicity on the course of drug transfer in (physiological) acceptor media. An increase in drug lipophilicity, according to ClogD/P values, was achieved by the formation of lipophilic prodrugs of 5-phenylanthranilic acid – a potential pathoblocker. The range of substances was supplemented by orlistat, lumefantrine and cholesteryl acetate as model drugs. Drug transfer from supercooled trimyristin nanodroplets was determined via differential scanning calorimetry by monitoring their onset crystallization temperature, which decreases linearly with increasing drug content. Release of the model (pro)drugs ranged from burst to hardly any release in the order of the ClogD/P values. Except for cholesteryl acetate, the results were in line with the lipophilicity of the model (pro)drugs estimated by their retention times on a reversed-phase HPLC column under isocratic conditions. An approximate prediction of drug release kinetics was, thus, possible by logP calculations and, to a limited extent, also by reversed-phase HPLC. A further finding was the increased drug loading capacity of the lipid nanoemulsion for lipophilic prodrugs, if the structural changes of the parent compound were accompanied by a lower melting point. [Display omitted] [ABSTRACT FROM AUTHOR]

Designing a wound dressing with controlled uptake, antibacterial, and proper biocompatibility is crucial for the appropriate wound healing process. In this study, alginate/tetracycline (Alg/TC) beads were produced and embedded into chitosan/pluronic/agarose semi-interpenetrating polymer network hydrogel, which serves as a potential biocompatible dressing for treating skin wounds. The effect of pluronic content on the porosity, swelling, mechanical characteristics, and degradation of the hydrogel was investigated. Furthermore, the impact of Alg beads on TC release was subsequently examined. In the absence of Alg beads, faster release was observed. However, after incorporating beads into the hydrogels, the release was sustained. Particularly, the hydrogel containing Alg beads exhibited a nearly linear release, reaching 74% after 2 days in acidic media. The antimicrobial activity and biocompatibility of the hydrogel were also evaluated to assess the capability of the TC-loaded hydrogels for wound dressing applications. The hydrogel demonstrated efficient antibacterial features against Gram-positive and Gram-negative bacteria. Additionally, the sample behavior was evaluated against exposure to yeast. Furthermore, based on biocompatibility studies using HFF2 cells, the TC-loaded hydrogel exhibited remarkable biocompatibility. Overall, this novel composite hydrogel shows remarkable biocompatibility and antibacterial activities which can be used as a great potential wound dressing to prevent wound infections due to its effective inhibition of bacterial growth. [ABSTRACT FROM AUTHOR]

The objective of this research was to create Tolbutamide extended-release (ER) tablets and evaluate their efficacy in comparison to the gold standard, hydrophobic polymer (HPC). The natural polymers that were considered for this study included guar gum, xanthan gum, acacia gum, and fenugreek mucilage. The mechanical characteristics, drug release patterns, and stability under accelerated settings of tablets produced employing direct compression at different polymer concentrations (25%, 50%, and 75%) were studied. With a release rate of 94.5 percent over 24 hours, the optimized formulation (TF6 with 75% Guar gum) offered the best sustained drug release. As for controlled-release qualities, Xanthan gum showed promise with a cumulative release of 93.45% and Acacia gum was dependable, though not quite as efficient. Fenugreek mucilage was not well suited for endotracheal formulations due to its rapid drug release. The optimized formulation (TF6) kept its mechanical integrity, drug content, and constant drug release profile throughout three months at 40°C/75% RH, according to stability testing. This study offers additional evidence that natural polymers, specifically Guar gum can effectively replace synthetic binders in sustained-release formulations. Additional research should explore alternative combinations of these natural binders to enhance formulation efficacy. [ABSTRACT FROM AUTHOR]

A novel pH sensitive antibiotic carrier hydrogel was synthesized having sustained drug releasing capabilities. The in-situ polymerization of Graphene oxide (GO), Polyvinyl pyrrolidone (PVP), and Carboxymethyl cellulose (CMC) of varying stoichiometry having Ca2+ as a linker yielded ternary nanocomposite hydrogels GO/PVP/CMC-II and GO/PVP/CMC-III. The physicochemical, structural, morphological and swelling properties of the binary nanocomposite GO/PVP and ternary nanocomposite hydrogels, GO/PVP/CMC were investigated using FTIR, XRD, SEM, TEM, TGA and DTA. FTIR and XRD confirm successive formation of ternary hydrogels. The hydrogels swelling studies at various pH levels viz. 4.5, 7 and 9.2, show that the swelling ability can be proportionally correlated with CMC concentration. To ensure the efficacy of this innovative hydrogel drug release application, an in vitro Ampicillin loading and release efficiency experiment at pH 7.2 (close to blood pH 7.3–7.5) was performed. Ternary hydrogels GO/PVP/CMC-II and GO/PVP/CMC-III exhibited sustained drug loading and release kinetics (72 h). [ABSTRACT FROM AUTHOR]

This research work dives into the complexity of hot-melt extrusion (HME) and its influence on drug stability, focusing on solid dispersions containing 30% of glibenclamide and three 50:50 polymer blends. The polymers used in the study are Ethocel Standard 10 Premium, Kollidon SR and Affinisol HPMC HME 4M. Glibenclamide solid dispersions are characterized using thermal analyses (thermogravimetric analysis (TGA) and differential scanning calorimetry), X-ray diffraction and scanning electron microscopy. This study reveals the transformation of glibenclamide into impurity A during the HME process using mass spectrometry and TGA. Thus, it enables the quantification of the extent of degradation. Furthermore, this work shows how polymer–polymer blend matrices exert an impact on process parameters, the active pharmaceutical ingredient's physical state, and drug release behavior. In vitro dissolution studies show that the polymeric matrices investigated provide extended drug release (over 24 h), mainly dictated by the polymer's chemical nature. This paper highlights how glibenclamide is degraded during HME and how polymer selection crucially affects the sustained release dynamics. [ABSTRACT FROM AUTHOR]

This study presents LHRH conjugated drug delivery via a magnetite nanoparticle-modified microporous Poly-Di-Methyl-Siloxane (PDMS) system for the targeted suppression of triple-negative breast cancer cells. First, the MNP-modified PDMS devices are fabricated before loading with targeted and untargeted cancer drugs. The release kinetics from the devices are then studied before fitting the results to the Korsmeyer–Peppas model. Cell viability and cytotoxicity assessments are then presented using results from the Alamar blue assay. Apoptosis induction is then elucidated using flow cytometry. The in vitro drug release studies demonstrated a sustained and controlled release of unconjugated drugs (Prodigiosin and paclitaxel) and conjugated drugs [LHRH conjugated paclitaxel (PTX+LHRH) and LHRH-conjugated prodigiosin (PG+LHRH)] from the magnetite nanoparticle modified microporous PDMS devices for 30 days at 37 °C, 41 °C, and 44 °C. At 24, 48, 72, and 96 h, the groups loaded with conjugated drugs (PG+LHRH and PTX+LHRH) had a significantly higher (p < 0.05) percentage cell growth inhibition than the groups loaded with unconjugated drugs (PG and PTX). Additionally, throughout the study, the MNP+PDMS (without drug) group exhibited a steady rise in the percentage of cell growth inhibition. The flow cytometry results revealed a high incidence of early and late-stage apoptosis. The implications of the results are discussed for the development of biomedical devices for the localized and targeted release of cancer drugs that can prevent cancer recurrence following tumor resection. [ABSTRACT FROM AUTHOR]

Developing bioequivalent (BE) generic products of complex dosage forms like intravitreal implants (IVIs) of corticosteroids such as dexamethasone prepared using hot-melt extrusion (HME), based on biodegradable poly (lactide-co-glycolide) (PLGA) polymers, can be challenging. A better understanding of the relationship between the physicochemical and physicomechanical properties of IVIs and their effect on drug release and ocular bioavailability is crucial to develop novel BE approaches. It is possible that the key physicochemical and physicomechanical properties of IVIs such as drug properties, implant surface roughness, mechanical strength and toughness, and implant erosion could vary for different compositions, resulting in changes in drug release. Therefore, this study investigated the hypothesis that biodegradable ophthalmic dexamethasone-loaded implants with 20% drug and 80% PLGA polymer(s) prepared using single-pass hot-melt extrusion (HME) differ in physicochemical and/or physicomechanical properties and drug release depending on their PLGA polymer composition. Acid end-capped PLGA was mixed with an ester end-capped PLGA to make three formulations: HME-1, HME-2, and HME-3, containing 100%, 80%, and 60% w/w of the acid end-capped PLGA. Further, this study compared the drug release between independent batches of each composition. In vitro release tests (IVRTs) indicated that HME-1 implants can be readily distinguished by their release profiles from HME-2 and HME-3, with the release being similar for HME-2 and HME-3. In the early stages, drug release generally correlated well with polymer composition and implant properties, with the release increasing with PLGA acid content (for day-1 release, R2 = 0.80) and/or elevated surface roughness (for day-1 and day-14 release, R2 ≥ 0.82). Further, implant mechanical strength and toughness correlated inversely with PLGA acid content and day-1 drug release. Drug release from independent batches was similar for each composition. The findings of this project could be helpful for developing generic PLGA polymer-based ocular implant products. [ABSTRACT FROM AUTHOR]

In recent years, mouse nerve growth factor (mNGF) has emerged as an important biological regulator to repair peripheral nerve injury, but its systemic application is restricted by low efficiency and large dosage requirement. These limitations prompted us to search for biomaterials that can be locally loaded. Oxidized sodium alginate hydrogel (OSA) exhibits good biocompatibility and physicochemical properties, and can be loaded with drugs to construct a sustained-release system that can act locally on nerve injury. Here, we constructed a sustained-release system of OSA-mouse nerve growth factor (mNGF), and investigated the loading and release of the drug through Fourier transform infrared spectroscopy and drug release curves. In vitro and in vivo experiments showed that OSA-mNGF significantly promoted the biological activities of RSC-96 cells and facilitated the recovery from sciatic nerve crush injury in rats. This observation may be attributed to the additive effect of OSA on promoting Schwann cell biological activities or its synergistic effect of cross-activating phosphoinositide 3-kinase (PI3K) through extracellular signal regulated kinase (ERK) signaling. Although the specific mechanism of OSA action needs to be explored in the future, the current results provide a valuable preliminary research basis for the clinical application of the OSA-mNGF sustained-release system for nerve repair. [ABSTRACT FROM AUTHOR]

The peritoneal cavity offers an attractive administration route for challenging-to-treat diseases, such as peritoneal carcinomatosis, post-surgical adhesions, and peritoneal fibrosis. Achieving a uniform and prolonged drug distribution throughout the entire peritoneal space, though, is difficult due to high clearance rates, among others. To address such an unmet clinical need, alternative drug delivery approaches providing sustained drug release, reduced clearance rates, and a patient-centric strategy are required. Here, we describe the development of a 3D-printed composite platform for the sustained release of the tyrosine kinase inhibitor gefitinib (GEF), a small molecule drug with therapeutic applications for peritoneal metastasis and post-surgical adhesions. We present a robust method for the production of biodegradable liposome-loaded hydrogel microbeads that can overcome the pharmacokinetic limitations of small molecules with fast clearance rates, a current bottleneck for the intraperitoneal (IP) administration of these therapeutics. By means of an electromagnetic droplet printhead, we 3D printed microbeads employing an alginate-based ink loaded with GEF-containing multilamellar vesicles (MLVs). The sustained release of GEF from microbeads was demonstrated. In vitro studies on an immortalized human hepatic cancer cell line (Huh-7) proved concentration-dependent cell death. These findings demonstrate the potential of 3D-printed alginate microbeads containing liposomes for delivering small drug compounds into the peritoneum, overcoming previous limitations of IP drug delivery. [ABSTRACT FROM AUTHOR]

Target drug delivery for therapeutic pharmaceuticals in a carcinogenic environment is becoming more popular because of its benefits, such as avoiding systemic adverse effects, high productivity and low-cost competence. Herein, in this study Evodiamine-albumin nanoparticles (EANPs) were incorporated into 3D porous polycaprolactone (PCL) scaffolds for sustained release, aiming to evaluate their potential as an effective and improved treatment for cervical cancer. Morphological and physicochemical analyses confirmed successful nanoparticle integration and drug amorphization. EANP-loaded scaffolds exhibited controlled drug release for 8 days, with increasing concentrations inducing dose-dependent cytotoxicity and apoptosis in HeLa cancer cells. These findings suggest EANP-loaded PCL scaffolds hold significant potential for improved cervical cancer treatment through sustained drug delivery and enhanced efficacy. [Display omitted] • Evodiamine-albumin nanoparticle (EANP) in polycaprolactone (PCL)3D scaffolds. • The characterization analysis of scaffold closely examined. • Drug release lasted 8 days, inhibiting HeLa cancer cells and dose-dependent too. • EANP-loaded PCL scaffold shows promise for cervical cancer therapy. [ABSTRACT FROM AUTHOR]

The present work aims to produce bacterial cellulose (BC) using Komagataeibacter hansenii, which was isolated after selective conditions in cultivation at 35 C, which were subjected to surface modifications through methanol treatment to produce membranes with different physical characteristics, which allow its use as device for sustained release of the antibacterial drug rifampicin (RIF) with broad spectrum and bactericidal activity against Gram-positive and Gram-negative species, being able to penetrate bacterial biofilms, for potential use as a dressing for the prevention or treatment of skin and soft-tissue infection (SSTI). Here, BC produced was treated with methanol (BC-MeOH) to obtain optimized membranes for use as sustained-release devices for the antibacterial RIF. Parameters such as fiber densities, thickness, and entanglement were assessed for BC-MeOH impregnated with RIF in methanolic solution (BC-MeOH-RIF) compared to BC in distilled water impregnated with RIF in an aqueous solution (BC-H2O-RIF) concerning the capacity for sustained release of RIF. BC-MeOH-RIF and BC-H2O-RIF were characterized by field emission scanning electron microscopy (FEG-SEM), thermogravimetric analysis (TGA), and Fourier transform infrared spectroscopy (FTIR). The comparison between the sustained release capacity of RIF by BC-RIF-MeOH and BC-RIF-H2O by applying the disc diffusion and Franz cell kinetics techniques demonstrated the ability of BC-RIF-MeOH to release, in a sustained manner, for 696 h uninterruptedly. Cell viability analysis showed that MeOH treatment did not interfere the development and adhesion of J774 cells, demonstrating the absence of cytotoxicity after heat treatment. Intermolecular interactions between RIF and BC were accounted for in water and methanol solutions using molecular dynamics simulations (MDS). Both FEG-SEM and MDS demonstrated that the interaction energy of the BC-RIF-MeOH set related to the RIF-BC is stronger in methanol solution than in water. These findings demonstrate that BC-RIF-MeOH can contribute to increase the therapeutic arsenal for bacterial infection treatment of SSTIs. [ABSTRACT FROM AUTHOR]

The study was aimed at formulating temozolomide (TMZ) loaded gelatin nanoparticles (GNPs) encapsulated into polyvinyl alcohol (PVA) nanofibers (TMZ–GNPs–PVA NFs) as the nano-in-nanofiber delivery system. The secondary objective was to explore the sustained releasing ability of this system and to assess its enhanced cellular uptake against U87MG glioma cells in vitro. Nano-in-nanofibers are the emerging drug delivery systems for treating a wide range of diseases including cancers as they overcome the challenges experienced by nanoparticles and nanofibers alone. The drug-loaded GNPs were formulated by one-step desolvation method. The Design of Experiments (DoE) was used to optimize nanoparticle size and entrapment efficiency. The optimized drug-loaded nanoparticles were then encapsulated within nanofibers using blend electrospinning technique. The U87MG glioma cells were used to investigate the uptake of the formulation. A 32 factorial design was used to optimize the mean particle size (145.7 nm) and entrapment efficiency (87.6%) of the TMZ-loaded GNPs which were subsequently ingrained into PVA nanofibers by electrospinning technique. The delivery system achieved a sustained drug release for up to seven days (in vitro). The SEM results ensured that the expected nano-in-nanofiber delivery system was achieved. The uptake of TMZ–GNPs–PVA NFs by cells was increased by a factor of 1.964 compared to that of the pure drug. The nano-in-nanofiber drug delivery system is a potentially useful therapeutic strategy for the management of glioblastoma multiforme. [ABSTRACT FROM AUTHOR]

Mucoadhesive microparticles for oromucosal drug delivery offer several advantages, including intimate contact with the mucosa, delivery to less accessible regions, extended residence time, sustained drug release, reduced irritation, and improved patient compliance. In this study, pullulan was used to prepare mucoadhesive spray-dried microparticles for delivering benzydamine hydrochloride (BZH) to oral mucosa. The BZH-pullulan spray-dried microparticles had a mean size of <25 μm with an angle of repose values between 25.8–36.6°. Pullulan markedly extended drug-release time to >180 min, ~9 times greater than the duration (i.e., 20 min) reportedly achieved by chitosan. Kinetic analysis showed the drug-release rate was concentration dependent and jointly controlled by drug diffusion and polymer chain relaxation. Further, pullulan was mucoadhesive and was able to retain up to 78.8% w/w of microencapsulated gold nanoparticle probes at the mucosal membrane. These data strongly suggest that BZH-pullulan microparticles have great potential for oromucosal drug delivery, by providing elongated residence time in situ and sustained drug release for the treatment of local diseases. [ABSTRACT FROM AUTHOR]

Fungal keratitis is a refractory eye disease that is prone to causing blindness. Fungal virulence and inflammatory responses are two major factors that accelerate the course of fungal keratitis. However, the current antifungal drugs used for treatment usually possess transient residence time on the ocular surface and low bioavailability deficiencies, which limit their therapeutic efficacy. In this work, natamycin (NATA)-loaded mesoporous zinc oxide (Meso-ZnO) was synthesized for treating Aspergillus fumigatus keratitis with excellent drug-loading and sustained drug release capacities. In addition to being a carrier for drug delivery, Meso-ZnO could restrict fungal growth in a concentration-dependent manner, and the transcriptome analysis of fungal hyphae indicated that it inhibited the mycotoxin biosynthesis, oxidoreductase activity and fungal cell wall formation. Meso-ZnO also promoted cell migration and exhibited anti-inflammatory role during fungal infection by promoting the activation of autophagy. In mouse models of fungal keratitis, Meso-ZnO/NATA greatly reduced corneal fungal survival, alleviated tissue inflammatory damage, and reduced neutrophils accumulation and cytokines expression. This study suggests that Meso-ZnO/NATA can be a novel and effective treatment strategy for fungal keratitis. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Novel delivery strategies are being explored since low bioavailability presents a challenge for medications like valsartan. Mucoadhesive drug delivery systems present a viable alternative by enhancing drug absorption and retention. Aim: This study aimed to develop mucoadhesive drug delivery systems to enhance the bioavailability of valsartan, leveraging a novel mucoadhesive polymer isolated from Samanea saman seeds. Materials and Methods: The study involved formulating oral mucoadhesive pellets by layering valsartan on starch pellets, followed by coatings of release-retardant polymer HPMC K15M and the novel Samanea saman gum. Optimization was achieved through response surface methodology, with assessments including mucoadhesive strength, drug release kinetics, compatibility studies, and pharmacokinetics evaluation. Results and Discussion: The optimized formulation, featuring 10% w/w HPMC K15M and 40% w/w Samanea saman gum coating, exhibited robust mucoadhesive strength and sustained drug release for 14 hr. Increasing Samanea saman gum concentration enhanced mucoadhesive strength and drug release retardation. Compatibility assessments confirmed the suitability of excipients, while microscopy and radiography revealed pellet integrity. Conclusion: The developed mucoadhesive drug delivery system effectively enhanced the bioavailability of valsartan, as evidenced by in vitro dissolution studies and in vivo pharmacokinetic studies in rats. This comprehensive approach offers a promising strategy for improving the therapeutic efficacy of valsartan through enhanced mucoadhesion and sustained release. [ABSTRACT FROM AUTHOR]

Berberine, a naturally occurring isoquinoline plant alkaloid molecule, finds application in traditional medicine due to its extensive pharmacological effects but it cannot be clinically exploited to its fullest as it possesses poor water solubility and bioavailability. In order to address this issue, we have synthesized berberine loaded chitosan nanoparticles (BCNPs) using DMSO as surfactant and chitosan as polymer using modified ionic complexation approach and optimized the process utilizing central composite design. The BCNPs were empirically assessed for various parameters such as particle size distribution, zeta potential, drug encapsulation efficiency and surface morphology using established methodologies. BCNPs were additionally assessed for in-vitro antibacterial activity, in-vitro antioxidant activity, in-vitro anti-inflammatory activity, and sustained drug release behavior using established techniques. Experimental results showed that chitosan at a concentration of 0.05 % (w/v) and DMSO at a concentration of 1 % (v/v) successfully generated nanoparticles with a spherical shape with size ranging from 20 to 60 nm and exhibited a stabilizing zeta potential of 26.1 mV. Additionally, they had a high encapsulation effectiveness of 94.01 %. Sustained release was observed with 74.30 % berberine released in 48 h, respectively from BCNPs. The antimicrobial assays reveal that BCNPs exhibit superior antibacterial effectiveness against all bacterial strains compared to berberine alone as determined by the agar well diffusion method. The BCNPs also exhibited a substantial enhancement in DPPH activity and a greater percentage of protection compared to berberine. In summary, our research suggests that chitosan nanocarrier can enhance the solubility of berberine and facilitate the development of novel naturally-derived antioxidants and anti-inflammatory compounds. This study will further provide an insight into the future development of natural drug discovery.

The combination of paclitaxel (PTX) with other chemotherapy drugs (e.g., gemcitabine, GEM) or genetic drugs (e.g., siRNA) has been shown to enhance therapeutic efficacy against tumors, reduce individual drug dosages, and prevent drug resistance associated with single-drug treatments. However, the varying solubility of chemotherapy drugs and genetic drugs presents a challenge in co-delivering these agents. In this study, nanoparticles loaded with PTX were prepared using the biodegradable polymer material poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx). These nanoparticles were surface-modified with target proteins (Affibody molecules) and RALA cationic peptides to create core-shell structured microspheres with targeted and cationic functionalization. A three-drug co-delivery system (PTX@PHBHHx-ARP/siRNAGEM) were developed by electrostatically adsorbing siRNA chains containing GEM onto the microsphere surface. The encapsulation efficiency of PTX in the nanodrug was found to be 81.02%, with a drug loading of 5.09%. The chemogene adsorption capacity of siRNAGEM was determined to be 97.3%. Morphological and size characterization of the nanodrug revealed that PTX@PHBHHx-ARP/siRNAGEM is a rough-surfaced microsphere with a particle size of approximately 150 nm. This nanodrug exhibited targeting capabilities toward BT474 cells with HER2 overexpression while showing limited targeting ability toward MCF-7 cells with low HER2 expression. Results from the MTT assay demonstrated that PTX@PHBHHx-ARP/siRNAGEM exhibits high cytotoxicity and excellent combination therapy efficacy compared to physically mixed PTX/GEM/siRNA. Additionally, Western blot analysis confirmed that siRNA-mediated reduction of Bcl-2 expression significantly enhanced cell apoptosis mediated by PTX or GEM in tumor cells, thereby increasing cell sensitivity to PTX and GEM. This study presents a novel targeted nanosystem for the co-delivery of chemotherapy drugs and genetic drugs.

Background: It is well known that periodontitis affects the gums and surrounding connective tissue. The chronic inflammatory response induced by bacteria in the gingival tissue leads to the loss of the collagen connection between the tooth and the bone and ultimately to bone loss. Methods: In this context, the aim of this research was the obtaining and characterization of a drug release supports in the form of sponges based on collagen, hyaluronic acid as a support and metronidazole as an antibiotic for the treatment of periodontitis. The sponges were characterized by FT-IR spectroscopy, water uptake, contact angle, SEM microscopy, in vitro metronidazole release analysis from sponges and data modeling. Results: The results showed that all the sponges had a porous structure with interconnected pores, the pore sizes being influenced by hyaluronic acid and metronidazole; the spongious structure became much more dense for samples with metronidazole content. All metronidazole-loaded sponges showed good surface wettability and an adequate swelling capacity for a suitable antimicrobial release at the periodontal pocket. The porous structures allow a controlled release, fast in the first hour, essential to control the initial microbial load at the periodontal level, which continues slowly in the following hours to ensure an effective treatment of periodontitis. Conclusions: Correlating all physical–chemical and bio-pharmaceutical results obtained, a promising solution for periodontitis treatment could be a met-ronidazole–collagen–hyaluronic system consisting of 1% collagen, 1.5% metronidazole and 0.8% hyaluronic acid, and in vitro and in vivo tests are recommended to continue studies.

Designing a wound dressing with controlled uptake, antibacterial, and proper biocompatibility is crucial for the appropriate wound healing process. In this study, alginate/tetracycline (Alg/TC) beads were produced and embedded into chitosan/pluronic/agarose semi-interpenetrating polymer network hydrogel, which serves as a potential biocompatible dressing for treating skin wounds. The effect of pluronic content on the porosity, swelling, mechanical characteristics, and degradation of the hydrogel was investigated. Furthermore, the impact of Alg beads on TC release was subsequently examined. In the absence of Alg beads, faster release was observed. However, after incorporating beads into the hydrogels, the release was sustained. Particularly, the hydrogel containing Alg beads exhibited a nearly linear release, reaching 74% after 2 days in acidic media. The antimicrobial activity and biocompatibility of the hydrogel were also evaluated to assess the capability of the TC-loaded hydrogels for wound dressing applications. The hydrogel demonstrated efficient antibacterial features against Gram-positive and Gram-negative bacteria. Additionally, the sample behavior was evaluated against exposure to yeast. Furthermore, based on biocompatibility studies using HFF2 cells, the TC-loaded hydrogel exhibited remarkable biocompatibility. Overall, this novel composite hydrogel shows remarkable biocompatibility and antibacterial activities which can be used as a great potential wound dressing to prevent wound infections due to its effective inhibition of bacterial growth.

Aim: The present research focused on development and optimization of ligand decorated theranostic nanocarrier encapsulating paclitaxel and carbon quantum dots (CQDs). Methods: CQDs were prepared by microwave-assisted pyrolysis and were characterized for particle size and fluorescence behavior. Ligand decorated zein nanoparticles, coloaded with paclitaxel and CQDs, were formulated using a one-step nanoprecipitation method and optimized for various process parameters. Results: Particle size for coated and uncoated nanoparticles was 90.16 ± 1.65 and 179.26 ± 3.61 nm, respectively, and entrapment efficiency was >80%. The circular dichroism spectroscopy showed zein retained its secondary structure and release study showed biphasic release behavior. Conclusion: The prepared theranostic nanocarrier showed optimal fluorescence and desired release behavior without altering the secondary structure of zein. [ABSTRACT FROM AUTHOR]

Acyclovir has a 10-30 % oral bioavailability with a half-life of 2-3 h. Acyclovir mainly gets solubilized in acidic conditions, and its absorption is found in the upper GIT. The primary aim of this research work was to formulate gastroretentive dosage form of acyclovir that can float on gastric content. The polymer used was sodium alginate, while the floating agent was calcium carbonate. The dependent variables of drug release, floating lag time and viscosity were significantly impacted by sodium alginate and CaCO3 concentrations. To assess the desired release pattern, a dissolution was performed in 0.1 N HCl at 50 rpm. Shear-thinning behaviour, instant gelation, 99.2 % drug release at 12 h, and instant floating ability greater than 12 h in 0.1 N HCl were all observed in the suspension. consequently, a sustained-release floating dosage form for acyclovir, with a duration of 12 h, was successfully developed. [ABSTRACT FROM AUTHOR]

The existing exenatide microspheres have the problem of burst release in the early stage, and minimal release in the middle stage which makes it difficult to achieve effective blood drug concentration (platform period). In this study, the modified exenatide microspheres were constructed to address the aforementioned issues. Poly(D,L-lactic-co-glycolic acid) (PLGA) and triblock copolymer with sol-gel conversion characteristics (PLGA-PEG-PLGA gel) were introduced as carriers to prepare microspheres. The hot gel characteristics and hydrophilicity of PLGA-PEG-PLGA gel were utilized to decline the burst release and shorten the platform period. Simultaneously, zinc acetate and exenatide were combined to generate an insoluble complex to further reduce the burst release. Herein, we prepared three types of exenatide microspheres using the solvent evaporation method and investigated their characterization as well as in vitro and in vivo release. According to the experimental findings, the modified exenatide microspheres, i.e., PLGA-PEG-PLGA gel and PLGA co-loaded zinc-exenatide insoluble complex microspheres (Zn-EXT-Gel-MS), had smooth and rounded surfaces, with a particle size of 24.7 μm, and the encapsulation rate reached 89.43%. And it was released for 40 days in vitro, behaving better than the other two microspheres in terms of release behavior. When this product was administered subcutaneously to rats, it produced a comparatively constant plasma exenatide concentration that lasted for 24 days and superior bioavailability than the exenatide microspheres (EXT-MS). The creation of modified exenatide microspheres may serve as a heuristic method for other long-acting medications. Schematic diagram of the synthesis process and release curves of three types of exenatide microspheres in vitro and in vivo [ABSTRACT FROM AUTHOR]

To overcome the limited application forms and inadequate therapeutic effects of 3D-printed scaffolds and osteogenic drug carriers. Nonetheless, concerns persist regarding the negative effects of burst and nonsustained release. In this study, we further enhanced the osteoinductive potential of 3D-printed BAG scaffolds by coating them with simvastatin (SIM) and poly(lactic-co-glycolic acid) (PLGA) with sustained release properties. Morphological assessment through SEM revealed evenly coated 3D-printed BAG scaffolds (BAG/PLGA/SIM), which showed sustained SIM release properties in vitro. The SIM released from BAG/PLGA/SIM still exhibited osteogenic activity in the augmentation of ALP activity and mineralization in mesenchymal stem cells. In an animal study of rat calvarial bone defects, both SIM-loaded BAG scaffolds, BAG/PLGA/SIM and BAG/PLGA/5 × SIM, significantly improved bone regeneration. Moreover, the IHC analysis of BMP2 and vWF expression also exhibited significant increases in both SIM-loaded BAG scaffolds. Notably, a higher SIM concentration (BAG/PLGA/5 × SIM) did not outperform a lower SIM concentration (BAG/PLGA/SIM) in promoting new bone formation. In conclusion, BAG/PLGA/SIM scaffolds could provide an excellent 3D architecture with sustained SIM release properties in vitro and excellent osteogenic properties for bone repair in vivo. The drug-loading method on 3D-printed BAG scaffolds could provide an alternative strategy for the development of multifunctional scaffolds for clinical applications.

The self-healing oxidized sodium alginate-glycol chitosan hydrogel (OSA-GC) based on dynamic imine bonds was synthesized. Oxidized sodium alginate (OSA) was synthesized by oxidizing sodium alginate with sodium periodate, and self-healing OSA-GC hydrogels with different cross-linking degrees were prepared by Schiff base reaction with glycol chitosan (GC). The effect of GC concentration on the microscopic morphology, viscoelasticity, swelling performance, self-repair performance, degradation rate and in vitro drug release performance of OSA-GC hydrogels were investigated. The results show that OSA-GC hydrogels have the characteristics of porous structure with a pore size ranging from 50 μm to 280 μm by controlling the mass ratio of OSA to GC. The OSA-GC hydrogels can reach the swelling equilibrium at 120 hours, and the swelling ratio reach 71.3-112.1. OSA-GC hydrogel can be degraded in PBS containing lysozyme (10 mg/mL), and the mass loss of OSA-GC hydrogel is 43.1%-51.9% after 12 days. At room temperature, OSA-GC hydrogels can achieve self-healing within 2 h in the absence of external stimuli. OSA-GC hydrogel loaded with gemcitabine shows a sustained release effect on the anti-cancer drug gemcitabine, and the release time can reach 48 hours in the drug release experiment, which shows promising application prospects in biomedical fields of drug carriers.

This research work dives into the complexity of hot-melt extrusion (HME) and its influence on drug stability, focusing on solid dispersions containing 30% of glibenclamide and three 50:50 polymer blends. The polymers used in the study are Ethocel Standard 10 Premium, Kollidon SR and Affinisol HPMC HME 4M. Glibenclamide solid dispersions are characterized using thermal analyses (thermogravimetric analysis (TGA) and differential scanning calorimetry), X-ray diffraction and scanning electron microscopy. This study reveals the transformation of glibenclamide into impurity A during the HME process using mass spectrometry and TGA. Thus, it enables the quantification of the extent of degradation. Furthermore, this work shows how polymer–polymer blend matrices exert an impact on process parameters, the active pharmaceutical ingredient’s physical state, and drug release behavior. In vitro dissolution studies show that the polymeric matrices investigated provide extended drug release (over 24 h), mainly dictated by the polymer’s chemical nature. This paper highlights how glibenclamide is degraded during HME and how polymer selection crucially affects the sustained release dynamics.

This study presents LHRH conjugated drug delivery via a magnetite nanoparticle-modified microporous Poly-Di-Methyl-Siloxane (PDMS) system for the targeted suppression of triple-negative breast cancer cells. First, the MNP-modified PDMS devices are fabricated before loading with targeted and untargeted cancer drugs. The release kinetics from the devices are then studied before fitting the results to the Korsmeyer–Peppas model. Cell viability and cytotoxicity assessments are then presented using results from the Alamar blue assay. Apoptosis induction is then elucidated using flow cytometry. The in vitro drug release studies demonstrated a sustained and controlled release of unconjugated drugs (Prodigiosin and paclitaxel) and conjugated drugs [LHRH conjugated paclitaxel (PTX+LHRH) and LHRH-conjugated prodigiosin (PG+LHRH)] from the magnetite nanoparticle modified microporous PDMS devices for 30 days at 37 °C, 41 °C, and 44 °C. At 24, 48, 72, and 96 h, the groups loaded with conjugated drugs (PG+LHRH and PTX+LHRH) had a significantly higher (p < 0.05) percentage cell growth inhibition than the groups loaded with unconjugated drugs (PG and PTX). Additionally, throughout the study, the MNP+PDMS (without drug) group exhibited a steady rise in the percentage of cell growth inhibition. The flow cytometry results revealed a high incidence of early and late-stage apoptosis. The implications of the results are discussed for the development of biomedical devices for the localized and targeted release of cancer drugs that can prevent cancer recurrence following tumor resection.

Copyright of Journal of Materials Engineering / Cailiao Gongcheng is the property of Journal of Materials Engineering Editorial Office 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.)

Copyright of Acta Materiae Compositae Sinica is the property of Acta Materiea Compositae Sinica Editorial Department 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.)

Respiratory antibiotics delivery has been appreciated for its high local concentration at the infection sites. Certain formulation strategies are required to improve pulmonary drug exposure and to achieve effective antimicrobial activity, especially for highly permeable antibiotics. This study aimed to investigate lung exposure to various inhalable ciprofloxacin (CIP) formulations with different drug release rates in a rat model. Four formulations were prepared, i.e., CIP-loaded PLGA micro-particles (CHPM), CIP microcrystalline dry powder (CMDP), CIP nanocrystalline dry powder (CNDP), and CIP spray-dried powder (CHDP), which served as a reference. The physicochemical properties, drug dissolution rate, and aerosolization performance of these powders were characterized in vitro. Pharmacokinetic profiles were evaluated in rats. All formulations were suitable for inhalation (mass median aerodynamic diameter < 5 µm). CIP in CHPM and CHDP was amorphous, whereas the drug in CMDP and CNDP remained predominantly crystalline. CHDP exhibited the fastest drug release rate, while CMDP and CNDP exhibited much slower drug release. In addition, CMDP and CNDP exhibited significantly higher in vivo lung exposure to CIP compared with CHDP and CHPM. This study suggests that lung exposure to inhaled drugs with high permeability is governed by drug release rate, implying that lung exposure of inhaled antibiotics could be improved by a sustained-release formulation strategy. [ABSTRACT FROM AUTHOR]

A platform mucoadhesive and thermogelling eyedrop was developed for application to the inferior fornix for the treatment of various anterior segment ocular conditions. The poly(n‐isopropylacrylamide) polymers (pNIPAAm), containing a disulfide bridging monomer, were crosslinked with chitosan to yield a modifiable, mucoadhesive, and natively degradable thermogelling system. Three different conjugates were studied including a small molecule for treating dry eye, an adhesion peptide for modeling delivery of peptides/proteins to the anterior eye, and a material property modifier to create gels with different rheologic characteristics. Based on the conjugate used, different material properties such as solution viscosity and lower critical solution temperature (LCST) were produced. In addition to releasing the conjugates through disulfide bridging with ocular mucin, the thermogels were shown to deliver atropine, with 70%–90% being released over 24‐h, depending on the formulation studied. The results illustrate that these materials can deliver multiple therapeutic payloads at one time and release them through various mechanisms. Finally, the safety and tolerability of the thermogels was demonstrated both in vitro and in vivo. The gels were instilled into the inferior fornix of rabbits and were shown to not produce any adverse effects over 4 days. These materials were demonstrated to be highly tunable, creating a platform that could be easily modified to deliver various therapeutic agents to treat a multitude of ocular diseases and have the potential to be an alternative to conventional eyedrops. [ABSTRACT FROM AUTHOR]

Purpose: As important challenges in burn injuries, infections often lead to delayed and incomplete healing. Wound infections with antimicrobial-resistant bacteria are other challenges in the management of wounds. Hence, it can be critical to synthesize scaffolds that are highly potential for loading and delivering antibiotics over long periods. Methods: Double-shelled hollow mesoporous silica nanoparticles (DSH-MSNs) were synthesized and loaded with cefazolin. Cefazolin-loaded DSH-MSNs (Cef*DSH-MSNs) were incorporated into polycaprolactone (PCL) to prepare a nanofiber-mediated drug release system. Their biological properties were assessed through antibacterial activity, cell viability, and qRT-PCR. The morphology and physicochemical properties of the nanoparticles and nanofibers were also characterized. Results: The double-shelled hollow structure of DSH-MSNs demonstrated a high loading capacity of cefazolin (51%). According to in vitro findings, the Cef*DSH-MSNs embedded in polycaprolactone nanofibers (Cef*DSH-MSNs/PCL) provided a slow release for cefazolin. The release of cefazolin from Cef*DSH-MSNs/PCL nanofibers inhibited the growth of Staphylococcus aureus. The high viability rate of human adipose-derived stem cells (hADSCs) in contact with PCL and DSH-MSNs/PCL was indicative of the biocompatibility of nanofibers. Moreover, gene expression results confirmed changes in keratinocyte-related differentiation genes in hADSCs cultured on the DSH-MSNs/PCL nanofibers with the up-regulation of involucrin. Conclusion: The high drug-loading capacity of DSH-MSNs presents these nanoparticles as suitable vehicles for drug delivery. In addition, the use of Cef*DSH-MSNs/PCL can be an effective strategy for regenerative purposes.

Mucoadhesive microparticles for oromucosal drug delivery offer several advantages, including intimate contact with the mucosa, delivery to less accessible regions, extended residence time, sustained drug release, reduced irritation, and improved patient compliance. In this study, pullulan was used to prepare mucoadhesive spray-dried microparticles for delivering benzydamine hydrochloride (BZH) to oral mucosa. The BZH-pullulan spray-dried microparticles had a mean size of 180 min, ~9 times greater than the duration (i.e., 20 min) reportedly achieved by chitosan. Kinetic analysis showed the drug-release rate was concentration dependent and jointly controlled by drug diffusion and polymer chain relaxation. Further, pullulan was mucoadhesive and was able to retain up to 78.8% w/w of microencapsulated gold nanoparticle probes at the mucosal membrane. These data strongly suggest that BZH-pullulan microparticles have great potential for oromucosal drug delivery, by providing elongated residence time in situ and sustained drug release for the treatment of local diseases.

[Display omitted] The objective of this study is to develop hydroxyapatite (HAp) particles for targeted delivery of honokiol to tumor sites after glioma surgical management. Honokiol is released from the HAp-honokiol particles inside cancer cells through endocytosis and subsequent acid lysosomal dissolution. HAp is synthesized using a co-precipitation method, and egg white is added to create porous structures. The HAp is then surface-modified with stearic acid to enhance its hydrophobicity and loaded with honokiol to form HAp-honokiol particles. The synthesized particles are of appropriate size and characteristics for cancer cell uptake. Honokiol remains attached on to the HAp particles in neutral environments due to its hydrophobic nature, but undergoes rapid burst release in acidic environments such as lysosomes. The HAp-honokiol treatment shows a delayed effect on cell viability and cytotoxicity, indicating sustained drug release without compromising drug efficacy. Flow cytometry analysis demonstrates the apoptosis pathway induced by HAp-honokiol in ALTS1C1 glioma cells. In the in vivo study using a mouse glioma model, MRI results showed a 40% reduction in tumor size after HAp-honokiol treatment. These findings suggest that HAp-honokiol particles have potential as an effective drug delivery system for the treatment of glioma. [ABSTRACT FROM AUTHOR]

Infiltrative glioma growth makes surgical excision incomplete, and the residual tumor cells proliferate rapidly. Residual glioma cells evade phagocytosis by macrophages through upregulating anti-phagocytosis molecule CD47, which binds to the signal regulatory protein alpha (SIRPα) of macrophages. Specifically, blocking the CD47-SIRPα pathway is a potential strategy for post-resection glioma treatment. In addition, the anti-CD47 antibody (α-CD47) in combination with temozolomide (TMZ) caused an enhanced pro-phagocytic effect due to the TMZ not only destroying DNA but also inducing endoplasmic reticulum stress response of glioma cells. However, the obstruction of the blood-brain barrier makes systemic combination therapy not ideal for post-resection glioma treatment. Herein, we designed a temperature-sensitive hydrogel system based on a moldable thermosensitive hydroxypropyl chitin (HPCH) copolymer to encapsulate both α-CD47 and TMZ as α-CD47&TMZ@Gel for in situ postoperative cavity administration. Through the in vitro and in vivo evaluations, α-CD47&TMZ@Gel significantly inhibited glioma recurrence post-resection through enhancement of pro-phagocytosis of macrophages, recruitment, and activation of CD8+ T cells and NK cells. [Display omitted] [ABSTRACT FROM AUTHOR]

Conventional eye treatment formulation such as eye drops has shortcomings including low drug utilization and poor patient compliance. The contact lens(CL), well-known as visual correction lens, is considered to be a more promising ophthalmic drug delivery vehicle owing to its good biocompatibility, long-term wearing comfort, prolonged drug residence time and improved bioavailability. In order to improve the drug loading efficiency and prolong the release time, researchers have developed a variety of strategies to modify traditional CL, including the introduction of vitamin E molecular barrier, application of molecular imprinting technology of CL, increasing interactions between the drug and polymer matrix by introducing special genes, and incorporation of nanocarriers or drug-loaded polymer films. In this paper, the preparation methods and pros and cons of drug-loaded CL are reviewed. At last, the existing problems and future developments of CL as ophthalmic drug delivery carrier are briefly discussed.

BACKGROUND: Quercetin plays a significant role in promoting osteogenesis, anti-allergy, anti-inflammatory, anti-oxidation, anti-virus, lowering blood pressure and anti-platelet aggregation, but its stability and solubility are poor, which is not conducive to the exertion and application of its efficacy. OBJECTIVE: To prepare quercetin sustained-release nanofibers for promoting bone formation and to investigate in vitro release mechanism of quercetin sustained-release nanofibers and its effect on the osteogenic properties of MC3T3-E1 cells. METHODS: Quercetin, bovine serum albumin, and chitosan were used as materials. The quercetin sustained-release nanofibers coated with chitosan were prepared by improved solvent removal method and electrospinning technology. The quercetin sustained-release nanofibers, polycaprolactone, and polyethylene glycol were utilized as materials. The quercetin sustained-release nanofiber scaffolds were prepared using electrospinning to characterize microscopic morphology, water contact angle, and in vitro drug release of nanofibers. Polycaprolactone/polyethylene glycol nanofiber scaffolds and quercetin sustained-release nanofibers were cocultured with MC3T3-E1 cells. The cells cultured alone were taken as blank controls. The proliferation and osteogenic differentiation abilities of the three groups were detected. RESULTS AND CONCLUSION: (1) Transmission electron microscopy showed that quercetin sustained-release nanospheres had smooth surface and uniform diameter. The microspheres could be effectively spun into the electrospinning scaffold. Scanning electron microscopy showed that the quercetin sustainedrelease nanospheres were regular spheres. The nanofibers were irregularly interwoven into a network structure and formed pores of different sizes without obvious fracture. (2) The contact angle experiment showed that the water contact angle of quercetin sustained-release nanofiber group was significantly smaller than that of polycaprolactone group and polycaprolactone/polyethylene glycol group. (3) The drug content released in the first 4 days reached about 30% in the quercetin sustained-release nanofiber group. The drug release time could be maintained for about one month, and the release amount could reach 70% of the drug content. (4) Compared with the blank control group, polycaprolactone/polyethylene glycol nanofibers and quercetin sustained-release nanofibers could promote MC3T3-E1 cell proliferation, alkaline phosphatase expression, and calcium deposition. (5) It is concluded that quercetin sustainedrelease nanofibers have a good controlled drug release effect and can promote the proliferation and osteogenic differentiation of MC3T3-E1 cells. [ABSTRACT FROM AUTHOR]

Ranibizumab is a recombinant VEGF-A antibody used to treat the wet form of age-related macular degeneration. It is intravitreally administered to ocular compartments, and the treatment requires frequent injections, which may cause complications and patient discomfort. To reduce the number of injections, alternative treatment strategies based on relatively non-invasive ranibizumab delivery are desired for more effective and sustained release in the eye vitreous than the current clinical practice. Here, we present self-assembled hydrogels composed of peptide amphiphile molecules for the sustained release of ranibizumab, enabling local high-dose treatment. Peptide amphiphile molecules self-assemble into biodegradable supramolecular filaments in the presence of electrolytes without the need for a curing agent and enable ease of use due to their injectable nature—a feature provided by shear thinning properties. In this study, the release profile of ranibizumab was evaluated by using different peptide-based hydrogels at varying concentrations for improved treatment of the wet form of age-related macular degeneration. We observed that the slow release of ranibizumab from the hydrogel system follows extended- and sustainable release patterns without any dose dumping. Moreover, the released drug was biologically functional and effective in blocking the angiogenesis of human endothelial cells in a dose-dependent manner. In addition, an in vivo study shows that the drug released from the hydrogel nanofiber system can stay in the rabbit eye's posterior chamber for longer than a control group that received only a drug injection. The tunable physiochemical characteristics, injectable nature, and biodegradable and biocompatible features of the peptide-based hydrogel nanofiber show that this delivery system has promising potential for intravitreal anti-VEGF drug delivery in clinics to treat the wet form age-related macular degeneration. [ABSTRACT FROM AUTHOR]

Purpose: As important challenges in burn injuries, infections often lead to delayed and incomplete healing. Wound infections with antimicrobial-resistant bacteria are other challenges in the management of wounds. Hence, it can be critical to synthesize scaffolds that are highly potential for loading and delivering antibiotics over long periods. Methods: Double-shelled hollow mesoporous silica nanoparticles (DSH-MSNs) were synthesized and loaded with cefazolin. Cefazolin-loaded DSH-MSNs (Cef*DSH-MSNs) were incorporated into polycaprolactone (PCL) to prepare a nanofiber-mediated drug release system. Their biological properties were assessed through antibacterial activity, cell viability, and qRT-PCR. The morphology and physicochemical properties of the nanoparticles and nanofibers were also characterized. Results: The double-shelled hollow structure of DSH-MSNs demonstrated a high loading capacity of cefazolin (51%). According to in vitro findings, the Cef*DSH-MSNs embedded in polycaprolactone nanofibers (Cef*DSH-MSNs/PCL) provided a slow release for cefazolin. The release of cefazolin from Cef*DSH-MSNs/PCL nanofibers inhibited the growth of Staphylococcus aureus. The high viability rate of human adipose-derived stem cells (hADSCs) in contact with PCL and DSH-MSNs/PCL was indicative of the biocompatibility of nanofibers. Moreover, gene expression results confirmed changes in keratinocyte-related differentiation genes in hADSCs cultured on the DSH-MSNs/PCL nanofibers with the up-regulation of involucrin. Conclusion: The high drug-loading capacity of DSH-MSNs presents these nanoparticles as suitable vehicles for drug delivery. In addition, the use of Cef*DSH-MSNs/PCL can be an effective strategy for regenerative purposes. [ABSTRACT FROM AUTHOR]

BACKGROUND: The number of patients with periodontitis increases year by year, and the use of traditional periodontal treatment cannot restore the periodontal soft and hard tissue. Therefore, it is necessary to prepare a drug sustained-release material to assist the treatment of periodontitis and restore the damaged soft and hard tissues of periodontitis. OBJECTIVE: To prepare bovine serum albumin microspheres composite hydrogel material, detect the dual sustained release effect on simvastatin, and further study the effect of the composite material on the adhesion and proliferation of osteoblasts. METHODS: (1) Bovine serum albumin microspheres loaded with simvastatin were prepared by solvent removal method. The morphology of microspheres was observed by transmission electron microscopy and scanning electron microscopy and the particle size of microspheres was measured. The encapsulation rate, drug loading rate and in vitro release of microspheres were detected by a microplate analyzer. (2) Simvastatin albumin microspheres were loaded into the prepared hydrogel, and in vitro drug release from hydrogels was detected using a microplate reader. The morphology of the composite material was observed by scanning electron microscopy. The hydrogel extract was used to culture MC3T3-E1 cells. The proliferation of osteoblasts was detected by CCK-8 assay. The alkaline phosphatase expression in osteoblasts was detected by alkaline phosphatase kit. RESULTS AND CONCLUSION: (1) Transmission electron microscopy showed that bovine serum albumin microspheres and blank microspheres loaded with simvastatin were smooth, spherical and dispersed, with no obvious aggregation. The particle size of bovine serum albumin microspheres was uniform, and 80% of the microspheres had a particle size between 0.2 μm and 0.8 μm. Scanning electron microscopy showed that the microspheres were smooth and spherical with good dispersion and uniform particle size distribution, ranging from 0.2 μm to 0.8 μm. (2) The encapsulation rate and drug loading rate of simvastatin microspheres were 68.9%-87.5% and 0.95%-1.21%, respectively. (3) Drug-loaded microspheres had the performance of gentle and sustained release of simvastatin. The release curve of simvastatin in the drug-loaded hydrogel is a fast release in the early stage and a slow sustained release process in the later stage, in which the drug-loaded hydrogel can release faster than the drug-loaded microspheres and reach the effective concentration of the drug. The slow release in the later stage maintains the concentration of the drug. (4) Scanning electron microscopy showed that the drug-loaded hydrogel had a porous striplike structure, which was suitable for the adhesion and growth of osteoblasts, and spherical drug-loaded microspheres could be seen on the surface of the hydrogel. (5) The drug-loaded hydrogel can promote the proliferation and alkaline phosphatase expression of MC3T3-E1 cells. (6) Simvastatin microspheres hydrogel composite had good biocompatibility and could promote the adhesion and proliferation of osteoblasts. [ABSTRACT FROM AUTHOR]

Scaffolds are implanted to spur the regeneration of damaged tissues. The inappropriate construction of scaffolds laden with cells is not efficient. The optimisation of the scaffolds' constituents is essential for tissue repair. In this study, a scaffold embedded with Raloxifene drug was optimised via Response Surface Methodology (RSM), targeting controlled cell proliferation. The independent variables for RSM (fibronectin, collagen I, glutaraldehyde, and Raloxifene) were screened in Swiss target prediction software (probability ≥99%) to optimise dependent variables (porosity, cell viability, degradation, and swelling) by ANOVA and characterised with FTIR, SEM and contact angle measurement. The scaffold was tested for antimicrobial property, and proliferation and attachment of mouse mesenchymal stem cells. The ANOVA analysis with p value ≤ 0.0001 suggested the optimal concentration of biomaterials and drugs. The optimised scaffold displayed 80% porosity with pore size 33 ± 3 µm. We also observed significant cell attachment and proliferation (p value ≤ 0.05) in optimised scaffold. The scaffold may be further evaluated for its potential for tissue repair. [ABSTRACT FROM AUTHOR]

Currently, the global increase in resistance of pathogens to widely used antibiotics requires a return to the practice of using some classic drugs with preserved activity, finding new ways and directions of delivery of antibiotics to the locations of pathogenic microorganisms and the use of antimicrobial drugs that are not yet resistant. Doxycycline refers to antimicrobial drugs that do not yet have widespread resistance. Numerous studies of doxycycline have now been described as enhancing therapeutic effects, including COVID-19-related diseases, and finding new delivery routes to limit systemic side effects associated with high doses and avoid antibiotic resistance. The aim of the work was to analyze modern ways of doxycycline delivery, to determine the prospects for use in pharmacy, to summarize and systematize data on its functional purpose in the development of drugs with specified pharmaco-technological parameters. It is established that in the Ukrainian pharmaceutical market the range of drugs based on doxycycline hyclate is represented only by solid oral dosage forms - tablets and capsules for immediate release, but in the global pharmaceutical market there are additional dosage forms that provide parenteral delivery of doxycycline and oral forms. suspensions, syrups, dispersed tablets and delayed-release dosage forms – tablets, capsules and granules, which are the basis for the development of domestic drugs based on doxycycline. Development of new dosage forms with modified DH, such as implants, aerosols, lyophilisate for solution for injection, development of new manufacturing technologies, selection of excipients and delivery systems can improve the pharmacological action of antibiotics by reducing the dose and frequency of administration, prolonged or controlled programming. , and expanding the range of therapeutic action. Doxycycline is promising in pharmaceutical practice for the treatment of COVID-19, both due to its ability to inhibit matrix metalloproteinases (MMPs) and antiviral activity, especially against Mycoplasma pneumoniae, which is a secondary bacterial cause of pneumonia during the COVID-19 pandemic.

In their recent publication, the authors explored the preventive effect of gentamicin in the irrigating solution on endophthalmitis caused by methicillin-resistant Staphylococcus epidermidis (MRSE) after phacoemulsification with intraocular lens (IOL) implantation in rabbits. This letter commends the authors for their innovative approach and discusses the potential of chitosan-based intraocular lenses as a future solution for reducing the incidence of endophthalmitis. Chitosan’s natural antibacterial properties, coupled with its capacity for sustained drug release and surface modification, make it a promising material for IOLs. This letter highlights recent advancements and suggests areas for further research to fully realize the potential of chitosan-based IOLs in ocular surgery. [ABSTRACT FROM AUTHOR]

Copyright of West China Journal of Stomatology is the property of Sichuan University, West China College of Stomatology 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.)

Invasive fungal infections increase mortality and morbidity rates worldwide. The treatment of these infections is still limited due to the low bioavailability and toxicity, requiring therapeutic monitoring, especially in the most severe cases. Voriconazole is an azole widely used to treat invasive aspergillosis, other hyaline molds, many dematiaceous molds, Candida spp., including those resistant to fluconazole, and for infections caused by endemic mycoses, in addition to those that occur in the central nervous system. However, despite its broad activity, using voriconazole has limitations related to its non-linear pharmacokinetics, leading to supratherapeutic doses and increased toxicity according to individual polymorphisms during its metabolism. In this sense, nanotechnology-based drug delivery systems have successfully improved the physicochemical and biological aspects of different classes of drugs, including antifungals. In this review, we highlighted recent work that has applied nanotechnology to deliver voriconazole. These systems allowed increased permeation and deposition of voriconazole in target tissues from a controlled and sustained release in different routes of administration such as ocular, pulmonary, oral, topical, and parenteral. Thus, nanotechnology application aiming to delivery voriconazole becomes a more effective and safer therapeutic alternative in the treatment of fungal infections. [ABSTRACT FROM AUTHOR]