Hydrogels For Drug Delivery Research Articles

Design and evaluation of fluorescent chitosan-starch hydrogel for drug delivery and sensing applications

Composite bio-based hydrogels have been obtaining a significant attention in recent years as one of the most promising drug delivery systems. In the present study, the preparation of composite chitosan-starch hydrogel using maleic acid as a cross-linker was optimized with the help of response surface methodology. The synthesized hydrogel was fluorescent owing to clustering of large number of functional groups. Different analytical techniques, including XRD, FTIR, SEM, XPS, fluorescence and BET were utilized to characterize the prepared hydrogel. XRD analysis confirmed the formation of non-crystalline hydrogel with random arrangement of macromolecular chains. The composite hydrogel exhibited good swelling percentage with pH sensitivity, hemocompatibility and degradability. BET analysis confirmed that the variation in concentration of crosslinker significantly influences the pore volume of the hydrogel. The synthesized composite chitosan-starch hydrogel was utilized as a prospective candidate for controlling drug release. Cefixime as a model drug was loaded onto the synthesized hydrogel utilizing the swelling diffusion method. SEM micrographs showed uniform distribution of drug molecules in the drug loaded hydrogel. In vitro drug release experiments indicated the swelling dependent drug release behaviour of chitosan-starch hydrogel with higher drug release at pH 7.4 (93.08 %) compared to pH 1.2 (67.85 %). The composite chitosan-starch hydrogel was able to prolong and control the drug release up to 12 h. The drug release from the hydrogel followed Korsmeyer-Peppas and Makoid-Banakar model with Fickian diffusion mechanism. Further, the composite hydrogel displayed excitation dependent fluorescence emission with most intense blue emission band at 425 nm with an excitation wavelength of 350 nm. The inclusion of cefixime drug in the hydrogel matrix significantly reduced the fluorescence intensity; the decrease was linearly correlated to the concentration of the drug. Moreover, the fluorescence emission the chitosan-starch hydrogel was found to be dependent upon pH. The synthesized hydrogel is expected to be a potential candidate for controlled drug release as well as for fluorescent sensing applications.

Preparation and drug delivery of hydrogels based on grafting of methacrylamide (MAAm) / vinylsulphonic acid (VSA) co monomers onto psyllium

Recently, a plethora of advancements have been made in the area of polysaccharide research to improve their properties for human health care. The present research is an attempt to develop hydrogels from through grafting of methacrylamide (MAAm) and vinyl sulphonic acid (VSA) co monomers onto psyllium for use in drug delivery (DD) applications. Copolymer hydrogels were characterized by scanning electron micrographs (SEM), Atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), 13C nuclear magnetic resonance (13C NMR), thermogravimetric analysis (TGA) and differential thermal analysis (DTG). SEM, AFM and XRD revealed heterogeneous morphology of the copolymer hydrogels with surface roughness and amorphous state of polymer chains in copolymer hydrogels due to graft-copolymerization reactions. The appearance of the FTIR bands at 1636.87 (amide-I), 1618.11 cm−1 (amide- II), 1469.58 cm−1 (amide- III) indicated presence of amide and bands at 1167.12 cm−1, 1112.06 cm−1 band (symmetric vibrations of SO3H groups and anti-symmetric & symmetric stretching modes of C–S) presence of VSA. The appearance of bands at 181.801 ppm and 62.053 ppm indicated presence of CO carbon of functional groups poly (MAAm) and −CH2–SO3H of poly (VSA) in copolymer hydrogels. Diffusion of the antibiotic drug vancomycin occurred in sustained manner with a non-Fickian diffusion mechanism. The release profile was best described by Korsmeyar-Peppas kinetic model. The copolymers exhibited biocompatible nature and revealed haemolytic index less than 5 % during polymer-blood interactions. The hydrogel demonstrated mucoadhesive character and required 0.135 ± 0.01 N force to detach from mucous membrane. These properties demonstrated the suitability of copolymer hydrogels for drug delivery applications.

In situ forming an injectable hyaluronic acid hydrogel for drug delivery and synergistic tumor therapy

Stimulus-responsive injectable hydrogel has the key characteristics of in situ drug-loading ability and the controlled drug release, enabling efficient delivery and precise release of chemotherapy drugs at the tumor site, thereby being used as a local drug delivery system for sustained tumor treatment. This article designed a smart responsive injectable hydrogel loaded with anti-tumor drugs and nanoparticles to achieve efficient and specific synergistic treatment of tumors. Hyaluronic acid (HA) hydrogel obtained by cross-linking HA-SH (HS) and HA-Tyr (HT) through horseradish peroxidase (HRP), and doxorubicin hydrochloride (DOX) and folic acid-polyethylene glycol-amine (FA-PEG-NH2) modified PDA (denoted as PPF) were encapsulated to construct the HS/HT@PPF/D hydrogel. The hydrogel had good biocompatibility, injectability, and could respond to multiple stimuli at the tumor site, thereby achieving controlled drug release. At the same time, PPF gave it excellent photothermal efficiency, photothermal stability and tumor targeting. In vitro and in vivo experimental results showed that the HS/HT@PPF/D hydrogel combined with near-infrared laser irradiation could significantly improve its anti-tumor effect and could almost eliminate the entire tumor mass without obvious adverse reactions. The HS/HT@PPF/D hydrogel could achieve multi-stimulus-responsive drug delivery and be used for precise chemo-photothermal synergistic tumor treatment, thus providing a new platform for local synergistic tumor treatment.

Alginate-Chitosan Biodegradable and Biocompatible Based Hydrogel for Breast Cancer Immunotherapy and Diagnosis: A Comprehensive Review.

Breast cancer is the most common type of cancer and the second leading cause of cancer-related mortality in females. There are many side effects due to chemotherapy and traditional surgery, like fatigue, loss of appetite, skin irritation, and drug resistance to cancer cells. Immunotherapy has become a hopeful approach toward cancer treatment, generating long-lasting immune responses in malignant tumor patients. Recently, hydrogel has received more attention toward cancer therapy due to its specific characteristics, such as decreased toxicity, fewer side effects, and better biocompatibility drug delivery to the particular tumor location. Researchers globally reported various investigations on hydrogel research for tumor diagnosis. The hydrogel-based multilayer platform with controlled nanostructure has received more attention for its antitumor effect. Chitosan and alginate play a leading role in the formation of the cross-link in a hydrogel. Also, they help in the stability of the hydrogel. This review discusses the properties, preparation, biocompatibility, and bioavailability of various research and clinical approaches of the multipolymer hydrogel made of alginate and chitosan for breast cancer treatment. With a focus on cases of breast cancer and the recovery rate, there is a need to find out the role of hydrogel in drug delivery for breast cancer treatment.

Impact of Peptide Length and Solution Conditions on Tetrameric Coiled Coil Formation.

Unlike naturally derived peptides, computationally designed sequences offer programmed self-assembly and charge display. Herein, new tetrameric, coiled coil-forming peptides were computationally designed ranging from 8 to 29 amino acids in length. Experimental investigations revealed that only the sequences having three or more heptads (i.e., 21 or more amino acids) exhibited coiled coil behavior. The shortest stable coiled coil sequence had a melting temperature (Tm) of approximately 58 ± 1 °C, making it ideal for thermoreversible assembly over moderate temperatures. Effects of pH and monovalent salt were examined, revealing structural stability over a pH range of 4 to 11 and an enhancement in Tm with the addition of salt. The incorporation of the coiled coil as a hydrogel cross-linker results in a thermally and mechanically reversible hydrogel. A subsequent demonstration of the hydrogel printed through a syringe illustrated one of many potential uses from 3D printing to injectable hydrogel drug delivery.

Application of alginate saline gel for drug delivery, cancer treatment and wound dressing

Application of alginate saline gel for drug delivery, cancer treatment and wound dressing

Effect of hydrogel drug delivery system for treating ulcerative colitis: A preclinical meta-analysis

Hydrogel drug delivery systems (DDSs) for treating ulcerative colitis (UC) have garnered attention. However, there is a lack of meta-analysis summarizing their effectiveness. Therefore, this study aimed to conduct a meta-analysis of pre-clinical evidence comparing hydrogel DDSs with free drug administration. Subgroup analyses were performed based on hydrogel materials (polysaccharide versus non-polysaccharide) and administration routes of the hydrogel DDSs (rectal versus oral). The outcome indicators included colon length, histological scores, tumor necrosis factor-α (TNF-α), zonula occludens protein 1(ZO-1), and area under the curve (AUC). The results confirmed the therapeutic enhancement of the hydrogel DDSs for UC compared with the free drug group. Notably, no significant differences were found between polysaccharide and non-polysaccharide materials, however, oral administration was found superior regarding TNF-α and AUC. In conclusion, oral hydrogel DDSs can serve as potential excellent dosage forms in oral colon −targeting DDSs, and in the design of colon hydrogel delivery systems, polysaccharides do not show advantages compared with other materials.

Nanofiber Hydrogel Drug Delivery System for Prevention of Postsurgical Intestinal Adhesion.

Intestinal adhesion is one of the complications that occurs more frequently after abdominal surgery. Postsurgical intestinal adhesion (PIA) can lead to a series of health problems, including abdominal pain, intestinal obstruction, and female infertility. Currently, hydrogels and nanofibrous films as barriers are often used for preventing PIA formation; however, these kinds of materials have their intrinsic disadvantages. Herein, we developed a dual-structure drug delivery patch consisting of poly lactic-co-glycolic acid (PLGA) nanofibers and a chitosan hydrogel (NHP). PLGA nanofibers loaded with deferoxamine mesylate (DFO) were incorporated into the hydrogel; meanwhile, the hydrogel was loaded with anti-inflammatory drug dexamethasone (DXMS). The rapid degradation of the hydrogel facilitated the release of DXMS at the acute inflammatory stage of the early injury and provided effective anti-inflammatory effects for wound sites. Moreover, PLGA composite nanofibers could provide sustained and stable release of DFO for promoting the peritoneal repair by the angiogenesis effects of DFO. The in vivo results indicated that NHP can effectively prevent PIA formation by restraining inflammation and vascularization, promoting peritoneal repair. Therefore, we believe that our NHP has a great potential application in inhibition of PIA.

Designing of tragacanth gum-poly(2-(methacryloyloxy) ethyl] dimethyl-(3-sulfopropyl) ammonium hydroxide) and poly(acrylamide) based hydrogels for drug delivery and wound dressing applications

Bioactive tragacanth gum (TG) was functionalized by covalent crosslinking of poly[2-(methacryloyloxy) ethyl] dimethyl-(3-sulfopropyl) ammonium hydroxide (PMEDSAH) to design network structure in form of hydrogel wound dressings (HWD). These copolymers were encapsulated with antibiotic drug vancomycin to enhance wound healing potential of the dressings. The copolymers were characterized by SEM, AFM, FTIR, 13C NMR, XRD, and TGA-DSC analysis. SEM demonstrated uneven heterogeneous morphology and AFM revealed rough surface of copolymer. Inclusion of synthetic component into HD was confirmed by FTIR and 13C NMR. Hydrogel dressings absorbed 8.49 ​± ​1.03 ​g/g simulated wound fluid and exhibited non-hemolytic (3.7 ​± ​0.02 % hemolytic potential) and antioxidant (37.42 ​± ​1.54 ​% free radical scavenging in DPPH assay) properties. Polymers required 35.0 ​± ​5.0 ​mN detachment force to get it detach from the mucosal surface during mucoadhesive test. Tensile strength was found to be 1.88 ​± ​0.13 ​N/mm2 during mechanical stability test. Hydrogel dressings were permeable to O2/H2O and impermeable to microbes. Release of drug vancomycin occurred through non-Fickian diffusion mechanism and release profile was best described by Korsmeyer-Peppas kinetic model. Overall, these results revealed that these hydrogels could be explored as materials for hydrogel wound dressings.

Complex hydrogel for cartilage regeneration and anti-inflammation

With the increasing incidence of osteoarthritis (OA) in elderly patients and the challenges posed by its multifaceted pathogenesis in developing effective treatments, this study explores the effective protein loading mode of Progranulin (PGRN) and its therapeutic potential for treating OA. GelMA hydrogels prepared with different concentrations of PGRN, employing AC-PEG-NHS as a crosslinking agent for drug encapsulation, were used to test the sustained release effect of the composite hydrogel drug delivery system. Additionally, we conducted in vitro assays to investigate the regulatory effects on rat bone marrow mesenchymal atromal cells (BMSCs), chondrocytes, and mouse macrophages - focusing on cell proliferation, and differentiation. For in vivo studies, histological staining techniques were utilized to assess inflammatory cell polarization and cartilage repair in a rat knee injury model. The results demonstrated that PGRN-loaded hydrogels significantly accelerated cell proliferation, enhance differentiation of BMSCs into chondrocytes, maintained a healthy chondrocyte phenotype, and induce M2-type polarization while inhibiting M1-type polarization in macrophages. Histological analyses also showed markedly improved tissue repair in the group treated with GelMA–NHS–PGRN hydrogels. As a result, these GelMA–NHS–PGRN hydrogels present a promising therapeutic approach for OA, potentially mitigating chronic inflammation and facilitating cartilage repair through controlled release of PGRN. Key worldPGRN, Osteoarthritis, Anti-inflammatory hydrogels, Cartilage regeneration.

Injectable Chitosan Hydrogels Doped with 2D Peptide Nanosheet-Drug Conjugates for Glutathione-Responsive Sustained Drug Delivery.

The development of novel and effective drug delivery systems aimed at enhancing therapeutic profile and efficacy of therapeutic agents is a critical challenge in modern medicine. This study presents an intelligent drug delivery system based on self-assembled two-dimensional peptide nanosheets (2D PNSs). Leveraging the tunable properties of amino acid structures and sequences, we design a peptide with the sequence of Fmoc-FKKGSHC, which self-assembles into 2D PNSs with uniform structure, high biocompatibility, and excellent degradability. Covalent attachment of thiol-modified doxorubicin (DOX) drugs to 2D PNSs via disulfide bond results in the peptide-drug conjugates (PDCs), which is denoted as PNS-SS-DOX. Subsequently, the PDCs are encapsulated within the injectable, thermosensitive chitosan (CS) hydrogels for drug delivery. The designed drug delivery system demonstrates outstanding pH-responsiveness and sustained drug release capabilities, which are facilitated by the characteristics of the CS hydrogels. Meanwhile, the covalently linked disulfide bond within the PNS-SS-DOX is responsive to intracellular glutathione (GSH) within tumor cells, enabling controlled drug release and significantly inhibiting the cancer cell growth. This responsive peptide-drug conjugate based on a 2D peptide nanoplatform paves the way for the development of smart drug delivery systems and has bright prospects in the future biomedicine field.

Recent advances in polymers, preparation techniques, applications and future perspectives of hydrogels

Drug delivery via hydrogel is one of the most effective methods. Hydrogels have been described as polymeric water-swollen materials and retain water in distinctive three-dimensional complex. These are classified as pH sensitive hydrogels, temperature sensitive hydrogels, homo-polymer hydrogels, co-polymer hydrogels and Interpenetrating Network (IP-N) hydrogel. Hydrogels can be prepared via various techniques, including physical crosslinking, chemical crosslinking, free radical polymerization, photo-initiator’s and hydrogen bonding. Various polymers in manufacturing includes pectin, chitosan, cyclodextrin and carrageenan, etc. This review aims to describes hydrogels for drug delivery, classifications, preparation techniques, various polymers in hydrogel preparation and highlights novel applications of hydrogels in medicine.

Triboelectric-Responsive Drug Delivery Hydrogel for Accelerating Infected Wound Healing.

Electrotherapy is of great interest in the field of tissue repair as an effective, well-tolerated, and noninvasive treatment. Triboelectric nanogenerator (TENG) has shown advantages in promoting wound healing due to its peak output characteristic and low Joule heating effect. However, it is limited in infected wound healing due to poor antimicrobial capacity. Here, a wearable triboelectric stimulator (WTS) is developed that consists of a flexible TENG (F-TENG) and a triboelectric-responsive drug delivery hydrogel (TR-DDH) for healing of bacterium-infected wounds. F-TENG can generate pulsed current to wounds by converting mechanical energy from body movements. Polypyrrole is prone to reduction and volume contraction under electrical stimulation, resulting in desorption of curcumin nanoparticles (CUR NPs) from the polypyrrole in TR-DDH. Therefore, the highly efficient and controllable release of CUR NPs can be achieved by triboelectric stimulation. According to the in vitro and in vivo experiments, WTS has the greatest antimicrobial effect and the fastest promotion of infected wound healing compared to treatment with electrical stimulation or curcumin. Finally, the safety assessment demonstrates that the WTS has excellent tissue safety for chronic wound healing. Synergistic therapy with WTS provides an efficient strategy for chronic wound healing and smart-responsive drug delivery systems.

Nanotechnology at Work: Hydrogel Drug Delivery Architectures

Hydrogels represent three-dimensional, interconnected networks known to absorb substantial amounts of H2O but at the same time, being insoluble in the aforementioned solvent. Their exceptional hydrophilic nature, biocompatibility and diverse therapeutic potential position them as highly promising biomaterials within biological and biomedical fields. These materials, on account of their innoxious innate characteristics and safe utilization, have garnered widespread acceptance across tremendous and diverse biomedical applications ranging from traditional therapies to state-of-the-art advancements. This extensive review incorporates a spectrum of varied types of hydrogels, elaborating on both their chemical, physical aspects and also throws light on the rheological, analytical and spectroscopic tools employed for their characterization. It also continues to elaborate on the various mechanisms of gelation for facilitating a better understanding of the topic under discussion. The review also discusses the different strategies which are substantiated in recent times to expand the utilisation of hydrogels. The primary intent of this review is to render a comprehensive understanding of hydrogels as an ideal drug delivery system to undergraduates, graduates, biomedical students and researchers across the globe. It also targets to unravel the fundamental, applied and general aspects of hydrogels, offering valuable insights to help individuals associated with multidisciplinary research and application spheres.
 Keywords: Gelation, Biocompatibility, Cross-linking, Smart hydrogels, Polymerization, Architecture, Polymer network

Development of Injectable Thermosensitive Nanocomposite Hydrogel for Ratiometric Drug Delivery to Treat Drug Resistant Chondrosarcoma In Vivo.

Chondrosarcoma(CS), a prevalent primary malignant bone tumor, frequently exhibits chemotherapy resistance attributed to upregulated anti-apoptosis pathways such as the Bcl-2 family. In this manuscript, a new strategy is presented to augment chemosensitivity and mitigate systemic toxicity by harnessing a nano-enabled drug delivery hydrogel platform. The platform utilizes "PLGA-PEG-PLGA", an amphiphilic triblock copolymer combining hydrophilic polyethylene glycol (PEG) and hydrophobic polylactide glycolide (PLGA) blocks, renowned for its properties conducive to crafting a biodegradable, temperature-sensitive hydrogel. This platform is tailored to encapsulate a ratiometrically designed dual-loaded liposomes containing a first-line chemo option for CS, Doxorubicin (Dox), plus a calculated amount of small molecule inhibitor for anti-apoptotic Bcl-2 pathway, ABT-737. In vitro and in vivo evaluations demonstrate successful Bcl-2 suppression, resulting in the restoration of Dox sensitivity, evident through impeded tumor growth and amplified necrosis rates at the tumor site. This delivery system showcases remarkable thermal responsiveness, injectability, and biodegradability, all finely aligned with the clinical demands of CS treatment. Collectively, this study introduces a transformative avenue for tackling drug resistance in CS chemotherapy, offering significant clinical potential.

Commercial hydrogel product for drug delivery based on route of administration.

Hydrogels are hydrophilic, three-dimensional, cross-linked polymers that absorb significant amounts of biological fluids or water. Hydrogels possess several favorable properties, including flexibility, stimulus-responsiveness, versatility, and structural composition. They can be categorized according to their sources, synthesis route, response to stimulus, and application. Controlling the cross-link density matrix and the hydrogels' attraction to water while they're swelling makes it easy to change their porous structure, which makes them ideal for drug delivery. Hydrogel in drug delivery can be achieved by various routes involving injectable, oral, buccal, vaginal, ocular, and transdermal administration routes. The hydrogel market is expected to grow from its 2019 valuation of USD 22.1 billion to USD 31.4 billion by 2027. Commercial hydrogels are helpful for various drug delivery applications, such as transdermal patches with controlled release characteristics, stimuli-responsive hydrogels for oral administration, and localized delivery via parenteral means. Here, we are mainly focused on the commercial hydrogel products used for drug delivery based on the described route of administration.

Tragacanth gum-based hydrogels for drug delivery and tissue engineering applications

Natural polymers have many uses, and Tragacanth gum is just one of them. Many people are interested in natural gums because of their many attractive characteristics, such as being ‘green’ bio-based renewable materials, being easily accessible, inexpensive, and structurally diverse. One class of naturally occurring polysaccharides is called gum because of its tendency to create a gel or a thick solution. Among the many plant-based raw materials, these polysaccharide gums are abundant. Hydrogels, which are three-dimensional polymeric webs that can imitate live tissues, have demonstrated remarkable potential as adjustable biomaterials in numerous regenerative techniques due to their high water or biological exudate absorption capacities. Natural polysaccharides, often known as gums, are present in many different types of trees and possess many desirable properties, such as being renewable, biocompatible, biodegradable, non-toxic, and amenable to chemical modification. Many people are curious about certain parts of the food, water, energy, biotech, environmental, and healthcare sectors as of now. Gum, a type of very important and unique food ingredient, has many vital uses in the food business. Cosmetics, coating, photosensitive resin, fertilizer, casting, pharmaceuticals, and tobacco are just a few of the non-food businesses that make use of their strong water-affinity and structural plasticity. There are a lot of benefits to hydrogels made from natural gums as opposed to those made from synthetic sources. Synthesis hydrogel polymers have been the center of interest among these non-food applications because of their extensive use in the pharmaceutical and medical fields. The Tragacanth gum hydrogels used for medication delivery and tissue engineering have been the focus of this study. We also paid close attention to drug delivery, physical-chemical properties, and the extraction of Tragacanth gum. Our research has a wide range of biomedical applications, including tissue engineering for bone, skin, fixation of bone, periodontal, and cartilage. Possible futures based on hydrogels made of Tragacanth gum were likewise our primary focus.

Preparation and sustained-release mechanism of hydroxybutyl chitosan/graphene oxide temperature-sensitive hypoglycaemic subcutaneous implants

The current situation of diabetes prevention and control is extremely severe. For instance, glimepiride (GLM), a third-generation sulfonylurea, demonstrates suboptimal clinical efficacy in oral dosage forms, which underscores the pressing need for the development of a new dosage form. Recently, in situ gel subcutaneous implants have garnered considerable attention. Hydroxybutyl chitosan (HBC) can spontaneously crosslink to form a thermosensitive hydrogel and has good biocompatibility. However, its application is hindered by its limited mechanical properties. Graphene oxide (GO), known for its stable dispersion in water, can load GLM through π–π stacking interactions. When combined with HBC, GO enhances the mechanical properties and stability of the hydrogel. Therefore, an HBC–GO@GLM hydrogel was prepared. Rheological analysis revealed that the incorporation of GO increased the critical gelation temperature of the 5 wt% HBC hydrogel from 19.1°C to 27.2°C, considerably enhancing the mechanical properties of the hydrogel. Using encapsulation efficiency as an evaluation index, the optimal encapsulation efficiency of GO@GLM was determined to be 73.53% ± 0.45% with a drug loading capacity of 27.39 ± 0.17% using the Box–Behnken design model. Computer simulation technology validated the interaction between the materials and the drug release mechanism. Pharmacokinetic results showed that compared to the HBC@GLM group, the half-life (t1/2), mean residence time and the area under the curve for the HBC–GO@GLM group were approximately 3 times those of the HBC@GLM group. Subcutaneous implantation of the HBC–GO@GLM hydrogel for drug delivery considerably extended the drug’s action time in the body, thereby maintaining blood sugar levels within a normal and stable range for an extended period.

Injectable pathological microenvironment-responsive anti-inflammatory hydrogels for ameliorating intervertebral disc degeneration

Chronic local inflammation and resulting cellular dysfunction of nucleus pulposus (NP) cells are important pathogenic factors of intervertebral disc degeneration (IDD). Injectable pathological microenvironment-responsive hydrogels hold significant potential for treating IDD by adapting to dynamic microenvironment of IDD. Herein, we proposed an injectable gelatin-based hydrogel drug delivery system that could respond to the pathological microenvironment of IDD for controlled release of anti-inflammatory drug to promote degenerative NP repair. The hydrogel system was prepared by conjugating phenylboronic acid-modified gelatin methacryloyl (GP) with the naturally extracted anti-inflammatory drug epigallocatechin-3-gallate (EGCG) through dynamic boronic esters. The hydrogel exhibited excellent degradability, injectability, antioxidant properties, anti-inflammatory effects, and biocompatibility. It also displayed responsive-release of EGCG under high reactive oxygen species (ROS) levels and acidic conditions. The hydrogel demonstrated remarkable cytoprotective effects on NP cells in both hyperactive ROS environments and inflammatory cytokine-overexpressed environments in vitro. In vivo studies revealed that the hydrogel injected in situ could effectively ameliorate the intervertebral disc degeneration by maintaining the disc height and NP tissue structure in a rat IDD model. The hydrogel system exhibited excellent biocompatibility and responsive-release of diol-containing drugs in pathological microenvironments, indicating its potential application as a drug delivery platform.

Intramyocardial delivery of injectable hydrogel with arctigenin alleviated myocardial ischemia-reperfusion injury in rats.

Arctigenin belongs to a major bioactive component of Fructus arctii and has been found with cardioprotective effects on rats with ischemia-reperfusion (I/R) injury. The application of arctigenin is limited due to poor water solubility and low bioavailability. Hydrogel drug delivery systems can improve the efficacy and safety of drugs, increase drug utilization, and reduce side effects. We hypothesized that hydrogels containing arctigenin would facilitate the effect of arctigenin and alleviate I/R injury in the rat heart. Presently, adult Sprague-Dawley (SD) rats were subjected to 1h of I/R injury, then hydrogels comprising arctigenin were implanted into the myocardium of rats. Triphenyl tetrazolium chloride staining, hematoxylin-eosin staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining and Western blot were performed for evaluating the infarct size, histopathological, and vital protein alterations of hearts. It was discovered that the hydrogel combined with arctigenin abated apoptosis and reduced infarct size. In addition, the results of echocardiography and Masson staining suggested that the hydrogel with arctigenin improved cardiac function, restrained myocardial fibrosis, and activated AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1). Collectively, the injectable hydrogel delivery system enhances the effect of arctigenin, which may play a protective role in I/R injury by activating AMPK and SIRT1.