Sustained Drug Delivery System Research Articles

Exploring the Effectiveness of Carboxymethylated and Crosslinked Albizia procera Gum in Diltiazem Hydrochloride Matrix Tablets: A Comparative Analysis.

This study investigates the efficacy of modified Albizia procera gum as a release-retardant polymer in Diltiazem hydrochloride (DIL) matrix tablets. Carboxymethylated Albizia procera gum (CAP) and ionically crosslinked carboxymethylated Albizia procera gum (Ca-CAP) were utilized, with Ca-CAP synthesized via crosslinking CAP with calcium ions (Ca2+) using calcium chloride (CaCl2). Fourier Transform (FT) IR analysis affirmed polymer compatibility, while differential scanning calorimetry (DSC) and X-ray diffraction (XRD) assessed thermal behavior and crystallinity, respectively. Zeta potential analysis explored surface charge and electrostatic interactions, while rheology examined flow and viscoelastic properties. Swelling and erosion kinetics provided insights into water penetration and stability. CAP's carboxymethyl groups (-CH2-COO-) heightened divalent cation reactivity, and crosslinking with CaCl2 produced Ca-CAP through -CH2-COO- and Ca2+ interactions. Structural similarities between the polymers were revealed by FTIR, with slight differences. DSC indicated modified thermal behavior in Ca-CAP, while Zeta potential analysis showcased negative charges, with Ca-CAP exhibiting lower negativity. XRD highlighted increased crystallinity in Ca-CAP due to calcium crosslinking. Minimal impact on RBC properties was observed with both polymers compared to the positive control as water for injection (WFI). Ca-CAP exhibited improved viscosity, strength, controlled swelling, and erosion, allowing prolonged drug release compared to CAP. Stability studies confirmed consistent six-month drug release, emphasizing Ca-CAP's potential as a stable, sustained drug delivery system over CAP. Robustness and accelerated stability tests supported these findings, underscoring the promise of Ca-CAP in controlled drug release applications.

Tissue engineered multifunctional chitosan-modified polypropylene hernia mesh loaded with bioactive phyto-extracts

Surface modified tissue engineered polypropylene / PP hernia meshes were fabricated by incorporating Bacterial cellulose / BC and chitosan / CS and phytochemical extracts. Under current practice, hernia and other traumatic injuries to the abdominal organs are clinically treated with surgical meshes. Often the foreign body reaction and infections result in relapse in patients which dictates additional reparative surgical procedures and pain. To improve the outcome of clinical restorative procedures new biomaterials with improved characteristics are required. The functionalized meshes were physically and chemically characterized using SEM, mechanical testing, FTIR and XRD. The antimicrobial activity was qualitatively and quantitatively tested using E. coli and S. aureus strains of bacteria. In vitro biocompatibility and wound healing effect of the modified meshes were performed using NIH3T3 fibroblast cell lines. Furthermore, tissue engineering potential of the meshes was evaluated using confocal fluorescent microscopy. In vivo implantation of the meshes was performed in male wistar rats for 21 days. Therefore, PP meshes with sustained drug delivery system augmented with anti-inflammatory and anti-microbial characteristics were developed. The coatings hereby not only increased the tensile strength of meshes but also prevented the modified meshes from causing infection. Current study resulted in CS-BC bioactive PP meshes loaded with phytochemicals which showed anti-inflammatory, antibacterial and wound healing potential. These meshes can be valuable to lessen the post-surgical complications of implanted PP mesh and thus reduce rejection and recurrence.

Yeast‐Controlled Double‐Shelled CaCO3/CaF2 Hollow Nanospheres with Hierarchically Porous for Sustained pH‐Sensitive Drug Release

Comprehensive SummaryHierarchically porous materials (HP materials) are believed one of the most hopeful matrix materials because of their distinctive multimodal pore structures and tremendous application potentials in the field of biomedicine. However, green and facile synthesis of hierarchically porous nanomaterials with beneficial water dispersibility and biocompatibility is still a great challenge. Herein, a novel biomimetic strategy is proposed to prepare the cell‐tailored double‐shelled HPCaCO3/CaF2 hollow nanospheres under the mediation of yeast cells. The biomolecules derived from the secretion of yeast cells are used as conditioning and stabilizing agents to control the biosynthesis of the HPCaCO3/CaF2 materials, which exhibit excellent water dispersibility and favorable biocompatibility. The double‐shelled CaCO3/CaF2 nanospheres hold hierarchically porous structure and have abundant pore channel and large specific surface area, showing high drug‐loading and a prolonged drug sustainable release profile by the pore‐by‐pore diffusion pattern of the hierarchical pores. Otherwise, the HPCaCO3 with pH‐sensitivity could controllably release drug doxorubicin hydrochloride (DOX) at the acidic tumor microenvironment. Both in vitro and in vivo results demonstrate that HPCaCO3/CaF2 has the sustainable pH‐sensitive drug release property, showing an enhanced therapeutic effect. Summarily, this study provides a biomimetic strategy to synthesize the hierarchically porous double‐shelled hollow nanomaterials for applying in sustainable drug delivery system.

Zwitterionic functionalization of polysaccharide gum by graft copolymerization to develop 3-D network materials for anticancer drug delivery applications

Herein, functionalization of polysaccharide gum has been carried out to develop network copolymeric materials for use in sustained anticancer drug delivery. Grafting reaction of poly[2-(methacryloyloxy)ethyl] dimethyl-(3-sulfopropyl)ammonium hydroxide (MEDSAH) onto sterculia gum has been done in the presence of crosslinker. Copolymeric materials were characterized by scanning electron micrographs (SEMs), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), 13C-nuclear magnetic resonance (NMR), and thermogravimetric analysis (TGA). SEM, AFM and XRD displayed heterogeneous morphology with a rough surfaces of amorphous copolymeric materials. Peaks at 173.822 ppm (carbonyl carbon) and at 60.653 ppm (methylene carbon attached to a quaternary ammonium group) confirmed the addition of poly(MEDSAH) during the grafting reaction. Mesh size in network hydrogel was found between 14.54 nm to 36.32 nm. Sustained release of doxorubicin was found with non-Fickian diffusion and was best demonstrated by the kinetic model Hixson Crowell. The biocompatibility of material was revealed in a haemolytic index (1.74 ± 0.26%) less than two percent during the copolymer-blood interaction. The material exhibited antioxidant and mucoadhesion properties. Free radical scavenging ability of copolymers was 49.41 ± 0.97% in 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay of the antioxidant test. These properties of copolymeric hydrogels demonstrated their suitability for use in sustained drug delivery systems for cancer chemotherapy.

Development of lactic acid based chain extender and soybean oil-derived polyurethanes for ecofriendly sustained drug delivery systems

In the present study, a range of sustainable, biocompatible and biodegradable polyurethanes (PU-1 to PU-4) were synthesized using different combinations of biobased polyol (obtained through the epoxidation of soybean oil, followed by ring opening with ethanol) and polyethylene glycol (PEG) and isophorone diisocyanate. The sustainable chain extender used in this study was synthesized by the esterification of lactic acid with ethylene glycol (EG). The synthesized PU samples were characterized through scanning electron microscopy (SEM), Fourier transformed infrared (FTIR) and nuclear magnetic resonance (1H NMR and 13C NMR) spectroscopy. Wetting ability and thermal degradation analysis (TGA) of the samples were also studied. Subsequently, these PUs were examined as potential drug delivery systems using Gabapentin as a model drug, which was loaded in the polymer matrix using the solvent evaporation method. The drug release studies were carried out in 0.06 N HCl as a release medium according to the method outlined in the United States Pharmacopeia. The maximum drug release was observed for sample PU-P1, which was found to be 53.0 % after 6 h. Moreover, a comparison of different PU samples revealed a trend wherein the values of drug release were decreased with an increase in the PEG content.

Functionalization of Arabinoxylan in Chitosan Based Blends by Periodate Oxidation for Drug Release Study

AbstractThis article presents the isolation of arabinoxylan (AX) from Plantago ovata seed husk and its oxidation using periodate to create oxidized‐AX (OAX) with distinct functionalities. Utilizing the solution casting method, biocompatible blends of arabinoxylan/chitosan (AX/CS) are prepared at various weight ratios, and their properties are assessed. Fourier transform infrared spectroscopy (FT‐IR), x‐ray diffraction (XRD), and thermogravimetric analysis (TGA) are employed to gauge compatibility and thermal traits of AX and OAX with CS. Solubility tests reveal partial and limited solubility of AX and OAX in distilled water, respectively. OAX displays favorable compressibility and flow rate through Carr's index, Hausner's ratio, and angle of repose analyses. FT‐IR data confirm intermolecular hydrogen bonding between CS′s −NH2− group and OAX′s carbonyl group, with XRD showing low crystallinity. Diclofenac sodium (DC) is loaded as a model drug into AX/CS and OAX/CS blends for release studies in pH 6.8 phosphate buffer. Results exhibit OAX/CS blends with sustained drug release, surpassing AX/CS blends. Among ratios tested, the OAX/CS (1 : 2) blend emerges as a superior excipient, demonstrating enhanced in‐vitro release potential, highlighting oxidized blends′ promise in sustained drug delivery systems.

Polydopamine-Modified Titanium Dioxide Nanotube Arrays Doped with Calcium as a Sustained Drug Delivery System.

Titanium nanotube (TNT) arrays manufactured via electrochemical anodization have been widely used as local drug carriers due to their excellent biocompatibility and customizable nanotubular structures. However, the uncontrollable and abrupt drug release at the early stage decreases the drug release duration, leading to excessive drug concentration at the implantation site. In this study, a continuous drug delivery system based on TNTs was created. Initially, a basic ultrasound-assisted approach was utilized to deposit a polydopamine (PDA) coating onto TNTs to obtain PDA-modified TNTs. Next, TNTs-PDA were submerged in a calcium chloride solution to include Ca2+ through Ca2+ coordination between the PDA layer's catechol groups. Sodium alendronate (NaAL) was used as a model drug and loaded onto TNTs-PDA-Ca2+ by immersing them in an NaAL solution. In the final step, NaAL was covalently attached to TNTs-PDA-Ca2+ through coordination bonds with Ca2+. The samples underwent characterization through the use of various techniques, including field emission scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction patterning, X-ray photoelectron spectroscopy, and inductively coupled plasma emission spectrometry. The results indicated that the bioactivity of TNTs improved, and there was an enhancement in drug loading capacity and release performance due to modification with PDA and Ca2+. Furthermore, acidic conditions can cause significant drug release due to the cleavage of coordination bonds between the drug and Ca2+ ions. Thus, the aforementioned drug delivery system represents a potentially promising approach for achieving sustained and controllable drug release.

RSM optimized chitosan based composite hydrogel for sustained drug delivery applications

Hybrid hydrogels with good biocompatibility have practical applications in the field of drug delivery. However, it remains challenging to formulate the hybrid hydrogels for sustained drug release by regulating their pore size and degradation rates. Herein, a hybrid chitosan-alginate hydrogel (superabsorbent) was synthesized using maleic acid as a cross-linker and acrylamide as a grafting agent. The composite hydrogel exhibited a good swelling percentage of 1246% (at pH 10), analysed using response surface methodology (RSM). The hybrid hydrogel system was hemocompatible as well as biocompatible and utilized for drug delivery applications. Pantoprazole sodium was taken as a model drug and it was loaded in the superabsorbent using the swelling diffusion method. The composite hydrogel showed excellent encapsulation efficiency for pantoprazole sodium (99.74%). The intermolecular interactions between hydrogel and drug were examined using different analytical techniques including XRD (X-Ray Diffraction), FTIR (Fourier transform infrared), SEM (Scanning electron microscope), thermal analysis and EDX (Energy dispersive X-ray) mapping. The swelling percentage of the drug loaded hydrogel under simulated gastrointestinal conditions was recorded as 917.80% (at stomach pH 1.2) and 756.95% (at intestinal pH 7.4) where protonation/deprotonation of the drug in the hydrogel matrix played an important role. In vitro drug release from the drug-loaded hydrogel was sustained up to 10 days and correlated with its swelling tendency, displaying higher release profiles at pH 1.2 (99.69%) than at pH 7.4 (72.16%). The pore volume of hydrogel was tuned varying the cross-linker amount during synthesis. BET (Brunauer-Emmett-Teller) results revealed that the pore volume of the hydrogel varied between 0.01775–0.01327 cm3/g for the cross-linker amount between 0.18–0.26 g, respectively. The impact of various factors including amount of cross-linker, pore volume, and drug loading percentage on drug release at pH 1.2 and 7.4 was studied statistically as well as experimentally and these factors significantly controlled the drug release percentage. The drug release from the hydrogel followed the Makoid-Banakar model with Fickian diffusion mechanism. The synthesized composite chitosan-alginate hydrogel could be a promising candidate for its utilization as a sustained drug delivery system.

Intestinal retentive systems - recent advances and emerging approaches.

Intestinal retentive devices (IRDs) are devices designed to anchor within the lumen of the intestines for long-term residence in the gastrointestinal tract. IRDs can enable impactful medical device technologies including sustained oral drug delivery systems, indwelling sensors, or real-time diagnostics. The design and testing of IRDs present a myriad of challenges, including precise deployment of the device at desired intestinal locations, secure anchoring within the gastrointestinal tract to allow for natural function, and safe removal of the IRD at user-defined times. Advancing the state-of-the-art of IRD is an interdisciplinary effort that requires innovations such as new materials, novel anchoring mechanisms, and medical device design with consistent input from clinical practitioners and end-users. This perspective briefly reviews the current state-of-the-art for IRDs and charts a path forward to inform the design of future concepts. Specifically, this article will highlight materials, retention mechanisms, and test beds to measure the efficacy of IRDs and their mechanisms. Finally, potential synergies between IRD and other medical device technologies are presented to identify future opportunities.

FORMULATION, DEVELOPMENT, AND EVALUATION OF OCUSERTS FOR QUINOLONE ANTIBIOTICS

Ophthalmic films are the best sustained-release ocular drug delivery system. The present study targets developing such ocular films of antibacterial with corticosteroid and evaluating its potential. Conventional ocular dosage forms have low bioavailability with low therapeutic response. The solvent cast method employed in ophthalmic films has triggered the minds of researchers to design sustained drug delivery systems overcoming pre-corneal constraints. The compatibility of antibacterial with Loteprednol Etabonate added polymers, excipients were evaluated through preformulation studies. Different combinations of ocular inserts with antibacterial drug and corticosteroid, excipients were formulated and evaluated. Formula CLE 80 (Ciprofloxacin Hydrochloride with Loteprednol Etabonate) fulfilled the needs of all organoleptic parameters like appearance, texture, surface pH, drug content, and in-vitro studies. The results predicted CLE 80 ophthalmic film would be a promising controlled-release formulation for better patient compliance

New metal-organic framework coated sodium alginate for the delivery of curcumin as a sustainable drug delivery and cancer therapy system

The utilization of biocompatible drug delivery systems with extended drug release capabilities is highly advantageous in cancer therapy, as they can mitigate adverse effects. To establish such a biocompatible system with prolonged drug release behavior, researchers developed an innovative drug carrier. In this study, a sustainable approach was employed to synthesize a new zinc-based metal-organic framework (Zn-MOF) through the reaction between synthesized Schiff base ligands and zinc ions. Comprehensive analyses, including FT-IR, XRD, SEM, BET surface area, and TGA techniques, were employed to thoroughly characterize the frameworks. Following comprehensive characterization, curcumin (CUR) was loaded onto the Zn-MOF, resulting in CUR entrapment efficiency and loading capacity of 79.23 % and 26.11 %, respectively. In vitro evaluations of CUR release from CUR@MOF exhibited controlled release patterns, releasing 78.9 % and 50.0 % of CUR at pH 5.0 and pH 7.4, respectively. To mitigate initial burst release, a coating of the biopolymer sodium alginate (SA) was applied to CUR@Zn-MOF. In vitro CUR release tests indicated that SA/CUR@Zn-MOF outperformed pristine CUR@Zn-MOF. The release of CUR conformed to the Korsmeyer-Peppas model, displaying non-Fickian diffusion. Furthermore, an in vitro cytotoxicity study clearly demonstrated the potent anti-tumor activity of the synthesized CUR@Zn-MOF attributed to its controlled release of CUR. This led to the induction of apoptotic effects and cell death across HeLa, HEK293, and SH-SY5Y cell lines. These findings strongly suggest that the developed pH-sensitive carriers hold remarkable potential as targeted vehicles for drug delivery in cancer therapy.

A comprehensive review on sustained release tablets

Sustained release is a method to reduce therapeutic drugs side effects by preventing the therapeutic concentration of the drug from fluctuating in the body. Sustained release is used to describe a pharmaceutical dosage form formulated to retard the release of therapeutic drug so that it remains in the systemic circulation for prolonged time and its plasma profile is sustained in duration. Sustained release drug delivery system has been formulated in form of tablets to slow down release of drug from tablets. It works on various mechanisms to control the release rate of drugs. Formulation approaches that have been utilized are drug dissolution, drug diffusion, matrix erosion. Present review work deals with the different aspect of the sustained release tablets.

Gastro Retentive ( Floating) Delivery System

Because of its flexibility in formulation, ease of administration, and patient compliance, the oral route of drug administration is the most preferred route. However, this route has some limitations, such as a limited gastric residence time (GRT) for sustained drug delivery systems and drugs that are absorbed from a specific region of the gastrointestinal tract (GIT). To overcome these limitations, various approaches to increasing the gastric retention time of the delivery system in the upper gastrointestinal tract have been proposed. The gastroretentive dosage form (GRDF) extends the GRT by directing drug release to the upper part of the GIT. GRDFs enable continuous and prolonged drug release and improve bioavailability of drugs with a narrow therapeutic window, thereby extending dosing intervals and increasing patient compliance. This article's goal is to compile the various gastroretentive approaches. We have summarized important factors controlling gastric retention in order to understand the various physiological difficulties in achieving gastric retention. Finally, the parameters for evaluating gastroretentive drug delivery systems are discussed. The current review briefly discusses the current state of various leading Until now, gastroretentive drug delivery technologies such as high density (sinking), floating, bio- or mucoadhesive, expandable, unfoldable, super porous hydrogel, magnetic systems, and so on have been developed. Furthermore, important factors controlling gastroretention, benefits, and future potential are discussed.

Recent advances in porous nanomaterials‐based drug delivery systems for osteoarthritis

AbstractOsteoarthritis (OA) is a common degenerative disease that develops over time, characterized mainly by inflammatory joints, cartilage deterioration, and ultimately loss of normal joint function. Some of the limitations that restrict the effectiveness of current OA treatment procedures include minimal penetration of medications into cartilage and lack of vascularity, leading to insufficient bioavailability and systemic toxicity. To increase the effectiveness of treatment, it is necessary to create novel non‐invasive OA treatment techniques. Porous nanomaterials (PNMs) show great promise as sustained drug delivery systems (DDSs) due to their functionality, variable porosity, and high loading capacity. In addition, they can provide targeted drug delivery, facilitate controlled release of drugs, and prolong drug circulation and retention time while reducing adverse reactions and improving drug solubility. First, the current treatment methods and challenges are summarized. Subsequently, recent advances in DDSs for OA treatment based on PNMs with various pore sizes and structures are presented. Lastly, the parameters that affect the performance of DDSs are discussed by giving some suggestions for their design. The purpose of this review is to provide new insights into PNM‐based DDS design and to inspire readers to adopt the smart design of intra‐articular DDSs in the future.

QbD assisted development of inhalable spray-dried erlotinib procubosomal system for the effective management of non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is the most common and leading cause of cancer deaths worldwide. Erlotinib (ERL), an epidermal growth factor receptor (EGFR) kinase inhibitor, has been used as a primary prescription for the effective treatment of metastatic NSCLC. However, it has poor aqueous solubility, extensive first-pass metabolism, oral administration-related toxicities, and inconveniences for cancer patients with gastrointestinal tract (GIT) disorders that limit its therapeutic potential. To resolve the above challenges, inhalable ERL-loaded spray-dried procubosomal powder (ERL-SDPP) was developed employing a Box-Behnken design that exhibit impressive characteristics including a device removal efficiency (DRE) of 84.7 ± 2.37 %, aerosolization efficiency (AE) of 18.1 ± 0.75, fine particle fraction (FPFTSI) of 33.7 ± 1.28 %, drug content (DC) of 93.6 ± 3.9 %, and a reconstituted cubosome size (PS) of 453.87 ± 14.65 nm. During in-vitro characterization, the optimized inhalable ERL-SDPP formulation was found to have 96.2 ± 3.98 % entrapment efficiency, −28.6 ± 1.38 mV zeta potential, and 3.29 ± 0.53 μm mass median aerodynamic diameter (MMAD). In-vitro drug release studies revealed sustained release behavior of ERL from ERL-SDPP lasting up to 36 h, demonstrating the increased dissolution profile and stability of ERL-SDPP in simulated lung fluids compared to pure ERL. In-vitro cytotoxicity studies utilizing A549 cell lines uncovered the greater potential of ERL-SDPP formulation, with a ∼1.5-fold reduction in IC50 compared to pure ERL, after 24 h treatment. In-vivo pharmacokinetic parameters revealed that inhalable ERL-SDPP exhibited a 1.76-fold and 6.25-fold higher AUC than oral and intravenous administered ERL, respectively. Organ distribution studies confirmed enhanced retention and accumulation of ERL in lungs after administration of inhalable ERL-SDPP compared to oral ERL, thereby reducing the dose and related systemic toxicities. Thus, the developed inhalable ERL-SDPP has shown promise to improve therapeutic potential against NSCLC through a site-specific sustained drug delivery system as it requires lower doses and limits systemic side effects.

Optimizing formulation parameters for the development of carvedilol injectable in situ forming depots

In situ forming depots (ISFDs) represent attractive alternatives to the conventional sustained drug delivery systems. Carvedilol, a short half-life drug used on a daily basis to manage chronic conditions, could benefit from this technology. The aim of this work was to develop, for the first time, a new injectable long-acting carvedilol-ISFD. Accordingly, 4 different grades of polyesters with varying properties as i) lactide-to glycolide ratio (polylactide-co-glycolide (PLGA) vs. polylactide (PLA)), and ii) end functionality (acid- vs. ester-capped) were utilized for the preparation of ISFD formulations. In addition, 4 different organic solvents with varying properties (i.e. N-methyl-2-pyrrolidone (NMP), dimethyl sulfoxide (DMSO), ethyl acetate, and benzyl benzoate) were also investigated. It was found that NMP and DMSO were more suitable for the formation of depots. Furthermore, all ISFD formulations demonstrated excellent encapsulation efficiency (i.e. 96–98%). Interestingly, both PLGA-based ISFDs (acid-capped and ester-capped) exhibited similar release behaviors and were able to extend carvedilol release over 30 days. On the other hand, acid-capped and ester-capped PLA-based ISFDs exhibited slower release over the 30 days with an average release of only 36% and 60%, respectively. In conclusion, the developed carvedilol-ISFDs resulted in a tunable extended-release behavior, simply by choosing the appropriate grade of polymer. These results open the door toward a novel injectable carvedilol-ISFD formulation.

Methyl-Branched Liposomes as a Depot for Sustained Drug Delivery.

Inadequate drug loading and control of payload leakage limit the duration of the effect of liposomal drug carriers and may cause toxicity. Here, we report a liposome system as a depot for sustained drug delivery whose design is inspired by the low permeability of Archaeal membranes to protons and solutes. Incorporating methyl-branched phospholipids into lipid bilayers decreased payload diffusion across liposomal membranes, thereby enhancing the drug load capacity by 10-16% and reducing the release of small molecules in the first 24 h by 40-48%. The in vivo impact of this approach was demonstrated by injection at the sciatic nerve. Methyl-branched liposomes encapsulating the anesthetic tetrodotoxin (TTX) achieved markedly prolonged local anesthesia lasting up to 70 h, in comparison to the 16 h achieved with liposomes containing conventional lipids. The present work demonstrates the usefulness of methyl-branched liposomes to enhance liposomal depot systems for sustained drug delivery.

Glucosamine-loaded injectable hydrogel promotes autophagy and inhibits apoptosis after cartilage injury

The ability of cartilage to regenerate and repair is limited. N-acetyl- d-glucosamine (GlcNAc) is a nutritional supplement commonly used to activate chondrocytes. To prolong the duration of action of GlcNAc and improve its curative effect after cartilage injury, a GlcNAc thermosensitive hydrogel is prepared based on Pluronic F127 (PF127). The physicochemical properties results indicate that this hydrogel is injectable and retards the release of GlcNAc. Further, the therapeutic benefits of GlcNAc hydrogel are detected through intra-articular injection in rat specimens with cartilage injury. Behavioral experiments results indicate that the rats treated with GlcNAc hydrogel had longer step lengths, smaller foot angles and slower fall times. Compared with the sham group, the expression of Sox9 was 1.5 times and the level of collagen II was 2.4 times in the hydrogel treated group. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining result confirmed that the GlcNAc hydrogel reduce apoptosis by about 50%. Our results of immunohistochemical staining, Western blotting assays and enzyme activity detection all suggested that GlcNAc hydrogel reduce the expression of cleaved-caspase3 and caspase8 (Compared to the sham group, the protein contents were reduced by about 50% in the GlcNAc hydrogel group). We also found that GlcNAc hydrogel activates autophagy through ERK signal pathway. The results of Western blotting indicated that GlcNAc hydrogel increase the levels of LC3B and Becline1 (hydrogel group & sham group, LC3B: 1.56 ± 0.07 & 1.00 ± 0.14; Becline1: 1.98 ± 0.07 & 1.00 ± 0.13). Whereas, the content of P62 reduced after GlcNAc hydrogel treatment, the relative level in sham group and hydrogel group are 1.00 ± 0.02 and 0.73 ± 0.06. Our results revealed that the number of P-ERK positive cells in the hydrogel group (57.36 ± 3.56%) was higher when compared with the sham (24.82 ± 2.72%). And, the ratio of P-ERK and ERK was higher than that in the sham group (1.48 ± 0.07 & 1.00 ± 0.08). The GlcNAc thermosensitive hydrogel is a promising and sustainable drug delivery system for intra-articular injection in the treatment of cartilage injury.

Transdermal Sustained Release Properties and Anti-Photoaging Efficacy of Liposome-Thermosensitive Hydrogel System.

Drug delivery systems have become a research priority in the biomedical field. The incorporation of liposomes to hydrogels further forms more robust multifunctional systems for more effective and sustained topical drug delivery. In this study, carboxymethyl-modified chitosan/hyaluronic acid (CMC/HA, CMH) thermosensitive hydrogel is developed for sustained transdermal delivery of liposomes. Hydrogels are crosslinked by hydrogen bonding, hydrophobic interaction and electrostatic interaction. The gel properties can be regulated by substitution degree (DS), and when DS = 18.20 ± 0.67% (CMH2), the gel temperature is 37.8°C, allowing rapid gelation at body temperature (315 s). Moreover, CMH2 hydrogel has suitable spreadability (17.7-57.2cm2 ), viscosity (2133.4mPas) and porous structure, which facilitated its adhesion and application on the skin and liposomes delivery. The hydrogel can retard the liposomesrelease, and the release rate of ascorbyl glucoside (AA2G)is 33.92-49.35% in 24h. Hydrogel avoids the rapid clearance of liposomes from the skin and improved the skin retention, achieving the long-term release of bioactive components. Liposome-hydrogel system more efficiently promotes the anti-photoaging effect of AA2G on skin, reducing epidermal thickness, melanin deposition and lipid oxidative damage and increasing collagen density. Therefore, liposome-hydrogel systems are proposed as multifunctional delivery systems for sustained transdermal delivery.

Recent progress in thermosensitive hydrogels and their applications in drug delivery area

AbstractThe scientific community has widely recognized thermosensitive hydrogels as highly biocompatible material with immense potential in drug delivery systems. When the temperature of these hydrogels approaches that of human body, a phase change occurs, enhancing their usefulness in a range of medical scenarios. This review article highlighted the background of thermosensitive hydrogels, their properties, and their applications in transdermal, oral, ophthalmic, intravaginal, nasal, rectal, cancer therapy, and cell‐loaded drug delivery systems. The literature suggests numerous advantages of these hydrogels over conventional drug delivery systems and find applications in various fields, such as therapeutic systems, filling processes, and sustained drug delivery systems. One of their key benefits is the ability to eliminate invasive procedures like surgery, providing a noninvasive alternative for drug administration. Moreover, they streamline the formulation process for both hydrophilic and hydrophobic drug delivery systems, simplifying the development of effective treatments. The thermosensitive hydrogels have been found to be green materials with negligible side effects and desirable drug delivery properties. The thermosensitive hydrogel's sustained‐release characteristics, immunogenicity, and biodegradability have also gained increased interest. Some of the disadvantages of thermosensitive hydrogels include delayed temperature response, weak mechanical characteristics, and poor biocompatibility, which limits their potential use in drug delivery applications.