Hydrogels For Release Research Articles

Ion-interferential cell cycle arrest for melanoma treatment based on magnetocaloric bimetallic-ion sustained release hydrogel

Melanoma treatment has been revolutionized with the development of targeted therapies and immunotherapies, which shows a positive influence on the patients. However, the long-term efficaciousness of such therapy is restricted by side effects, limited clinical effects as well as quick resistance to treatment. In this work, we prepared magnetocaloric carrier-free bimetallic hydrogels, named manganese-iron oxide nanocubes@polyethylene glycol-hydrogels (MFO@PEG-Gels), to realize ion-interferential cell cycle arrest for melanoma treatment. In detail, the tumor site was exposed to alternating magnetic field (AMF) after intratumorally injected MFO@PEG-Gels, which generated hyperthermia and promoted the sol-gel phase transition for MFO sustained release. Under the tumor microenvironment, hydrogen peroxide triggered MFO degradation to induce Mn2+ and Fe3+ release. On one hand, Mn2+ blocked G1/S phase through the activation of p27 pathway. On the other hand, Fe3+ could arrest the G2/M phase by upregulating the polo-like kinase 4 (PLK4) expression as well as inhibiting autolysosome formation to achieve the enhanced cell cycle arrest, thereby promoting the apoptosis of melanoma cells. In summary, this study proposed ion-interferential cell cycle arrest strategy by a multifunctional and injectable magnetic bimetallic hydrogel for melanoma treatment, which provided a secure and sustainable regimen for enhancing anti-tumor efficacy.

Dual Growth Factor Delivery Using Photo-Cross-Linkable Gelatin Hydrogels for Effectively Reinforced Regeneration of the Rotator Cuff Tendon.

Rotator cuff tears are currently treated with drugs (steroids and nonsteroidal anti-inflammatory drugs) and surgery. However, the damaged rotator cuff requires a considerable amount of time to regenerate, and the regenerated tissue cannot restore the same level of function as that before the damage. Although growth factors can accelerate regeneration, they are difficult to be used alone because of the risk of degradation and the difficulties in ensuring their sustained release. Thus, hydrogels such as gelatin are used, together with growth factors. Gelatin is a biocompatible and biodegradable hydrogel derived from collagen; therefore, it closely resembles the components of native tissues and can retain water and release drugs continuously, while also showing easily tunable mechanical properties by simple modifications. Moreover, gelatin is a natural biopolymer that possesses the ability to form hydrogels of varying compositions, thereby facilitating effective cross-linking. Therefore, gelatin can be considered to be suitable for rotator-to-tendon healing. In this study, we designed photo-cross-linkable gelatin hydrogels to enhance spacing and adhesive effects for rotator cuff repair. We mixed a ruthenium complex (Ru(II)bpy32+) and sodium persulfate into gelatin-based hydrogels and exposed them to blue light to induce gelation. Basic fibroblast growth factor and bone morphogenetic protein-12 were encapsulated in the gelatin hydrogel for localized and sustained release into the wound, thereby enhancing the cell proliferation. The effects of these dual growth factor-loaded hydrogels on cell cytotoxicity and tendon regeneration in rotator cuff tear models were evaluated using mechanical and histological assessments. The findings confirmed that the gelatin hydrogel was biocompatible and that treatment with the dual growth factor-loaded hydrogels in in vivo rotator cuff tear models promoted regeneration and functional restoration in comparison with the findings in the nontreated group. Therefore, growth factor-loaded gelatin-based hydrogels may be suitable for the treatment of rotator cuff tears.

Polyurethane based thin hydrogels for sustained protein delivery

The development of materials that allow the sustained release of therapeutic proteins is the key feature for improving their pharmacokinetics, bioavailability, and dose reduction. In this context, hydrogels are attracting interest, but their design to provide a sustained release profile is still a challenge. Usually, a large mass of polymer is required to prolong the release of the therapeutic agent, involving hydrogels with high thicknesses, which limits their use in some applications. Here, the synthesis of thin thermoresponsive and functionalized hydrogels (tHGs) for sustained protein release is reported to tackle this problem. tHGs were obtained by photo-crosslinking of linear thermoresponsive polyurethanes (PU) based on polyethilenglycol and a functional diol (methyldiethanolamine) that contribute to tertiary amine functionality. These biocompatible tHGs conserved the thermosensitive property of PU, exhibiting a reversible volume change between the swollen and the collapsed state, as a function of temperature. tHGs were able to load the model protein ovalbumin homogenously in their matrix, and sustainably release it during 25 days with a tuneable profile, by changing the PU composition. Finally, this proposal, which combined a very thin delivery film with a sustained protein release, could be a good candidate for its application in ocular therapy.

Gelatin extracted from chromium (III) tanned leather waste for the synthesis of controlled release hydrogel

Chromium (III) tanned leather wastes were used to obtain gelatin, which was applied as a coating material for the synthesis of controlled urea release hydrogels. It was found that the hydrogel released its total urea content in 120 h in aqueous solution and that it promoted a significant difference in the growth of arugula seedlings. When compared with commercial gelatin, the hydrogels based on gelatin extracted from tannery waste had similar behavior, especially in the way urea was diffused to the external environment of the controlled release system, it can be characterized as a material of non-Fickian behavior during the swelling process and later, as a Fickian behavior, when it begins its process of degradation of the polymer matrix. In this way, this work demonstrates that it is possible to value a waste to obtain tools to promote a more sustainable agriculture.

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.

Engineering Hydrogels for Affinity-Based Release of Therapeutic Proteins

Engineering Hydrogels for Affinity-Based Release of Therapeutic Proteins

CCD-optimized Moringa oleifera-based hydrogel for the targeted and controlled release of the anti-cancer drug Raloxifene: evaluation of hemocompatible, cytotoxic and antioxidant properties

Naturally extracted Moringa oleifera gum has been utilized to synthesize a Moringa oleifera gum-based hydrogel for the pH-responsive sustained release of the anti-cancer drug Raloxifene.

A photocrosslinkable and anti-inflammatory hydrogel of loxoprofen-conjugated chitosan methacrylate.

Polymer-drug conjugates are widely used for drug delivery. Herein, we report an injectable hydrogel for local delivery of nonsteroidal anti-inflammatory drugs (NSAIDs) using chitosan (CS) as a carrier polymer. Loxoprofen (LOX) was conjugated to the backbone of CS via carbodiimide chemistry to obtain the LOX-CS conjugate. This conjugation transformed the water-insoluble unmodified CS into the water-soluble LOX-CS conjugate. In particular, the LOX-CS conjugate did not precipitate at pH 7, allowing smooth subsequent chemical modification with methacrylic anhydride (MA) to synthesize LOX-CS methacrylate (LOX-CS-MA) with significantly higher methacrylation substitution. The LOX-CS-MA was capable of in situ gel formation under visible light irradiation in the presence of a benzoin-2,4,6-trimethylbenzoylphosphinate lithium (LAP) photoinitiator. Our results show that the LOX-CS-MA hydrogel exhibited good cytocompatibility and blood compatibility. It promoted M2 polarization, inhibited pro-inflammatory gene expression, and upregulated anti-inflammatory gene expression of macrophages. Furthermore, the LOX-CS-MA hydrogel significantly reduced reactive oxygen species (ROS) and nitric oxide (NO) produced by lipopolysaccharide (LPS)-stimulated macrophages. A subcutaneous implanted LOX-CS-MA hydrogel in a rat model revealed significantly reduced inflammatory cell density, decreased cell infiltration, and a much thinner fibrous capsule compared to the CS methacrylate (CS-MA) hydrogel, thus markedly alleviating the inflammatory response. This study highlights the feasibility of CS-drug conjugates in preparing CS-based methacrylate hydrogels for sustained drug release.

Injectable and NIR-responsive CDN-POM hydrogels for combined non-inflammatory photo-immunotherapy.

Similar to clinically applied thermal ablation techniques, the cellular necrosis that occurs during photothermal tumor therapy (PTT) can induce inflammatory response, severely compromising the therapeutic efficacy and clinical translation of the PTT. Inspired by the remarkable ROS-scavenging activity and high photothermal efficiency of molybdenum-based polyoxometalate (POM) and the immunostimulatory effect of cyclic dinucleotides (CDNs), a NIR-responsive and injectable DNA-mediated hybrid hydrogel (CDN-POM) has been developed. The hydrogels have superior photothermal efficiency (43.41%) to POM, impressive anti-inflammatory capability and prolonged intratumoral CDN-releasing behavior, thus enabling synergistic anti-tumor therapeutic outcomes. Meanwhile, local treatment induced by CDN-POM hydrogels displays minimal side effects on normal tissue. Taking advantage of the high phototherapeutic effect, ROS-scavenging activity and sustained CDN release of CDN-POM hydrogels, a novel combined approach that integrates photothermal therapy and immunotherapy of breast tumor is successfully pioneered.

Comparative Proteomics Inspired Self-Stimulated Release Hydrogel Reinforces the Therapeutic Effects of MSC-EVs on Alzheimer's Disease.

The clinical application of extracellular vesicles (EVs)-based therapeutics continues to be challenging due to their rapid clearance, restricted retention, and low yields. Although hydrogel possesses the ability to impede physiological clearance and increase regional retention, it typically fails to effectively release the incorporated EVs, resulting in reduced accessibility and bioavailability. Here an intelligent hydrogel in which the release of EVs is regulated by the proteins on the EVs membrane is proposed. By utilizing the EVs membrane enzyme to facilitate hydrogel degradation, sustained retention and self-stimulated EVs release can be achieved at the administration site. To achieve this goal, the membrane proteins with matrix degrading activity in the mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are identified using comparative proteomics. After that, a hydrogel comprised of self-assembled peptides that are susceptible to degradation by the membrane enzymes present in MSC-EVs is designed and synthesized. After intranasal administration, this peptide hydrogel facilitates sustained and thermo-sensitive release of MSC-EVs, thereby extending the retention of the MSC-EVs and substantially enhancing their potential for treating Alzheimer's disease. This research presents a comparative proteomics-driven approach to intelligent hydrogel design, which holds the capacity to significantly enhance the applicability of EVs in clinical settings.

Fabrication of Interpenetrating Polymer Network-Based Hydrogel for Colon-Targeted Release of Nateglinide

Nateglinide is an anti-diabetic agent that experiences modest first-pass metabolism and poor aqueous solubility. This paper explores the preparation, characterization, and evaluation of interpenetrating polymer network composite hydrogels of chitosan and poly(meth(methacrylic)) acid as a potential carrier for the drug. Interpenetrating polymer network composite hydrogels of chitosan and poly(meth(methacrylic) acid incorporating nateglinide were prepared using N,Nꞌ-methylene bisacrylamide and glutaraldehyde as cross-linkers. The polymerization of chitosan, entrapment of the drug, and its interaction in prepared hydrogels were checked by FTIR spectroscopy, DSC, and powder XRD studies. The hydrogels were evaluated for their swelling behavior and in vitro drug release. The morphology of the hydrogels before and after dissolution was studied using SEM. The hydrogels showed a 93.29 ± 4.65% yield and 91.28 ± 2.22% drug loading. The hydrogels exhibited pH-sensitive swelling behavior. The in vitro release profile confirmed that the drug release depended on the swelling of hydrogels and showed a biphasic release pattern. Chitosan-poly(meth(methacrylic)) acid interpenetrating polymer network hydrogel, with its biodegradable nature and pH-sensitive release of nateglinide, is an attractive option to be further explored for targeted controlled drug delivery formulations for the drug.

ROS-Responsive 4D Printable Acrylic Thioether-Based Hydrogels for Smart Drug Release.

Reactive oxygen species (ROS) play a key role in several biological functions like regulating cell survival and signaling; however, their effect can range from beneficial to nondesirable oxidative stress when they are overproduced causing inflammation or cancer diseases. Thus, the design of tailor-made ROS-responsive polymers offers the possibility of engineering hydrogels for target therapies. In this work, we developed thioether-based ROS-responsive difunctional monomers from ethylene glycol/thioether acrylate (EGnSA) with different lengths of the EGn chain (n = 1, 2, 3) by the thiol-Michael addition click reaction. The presence of acrylate groups allowed their photopolymerization by UV light, while the thioether groups conferred ROS-responsive properties. As a result, smart PEGnSA hydrogels were obtained, which could be processed by four-dimensional (4D) printing. The mechanical properties of the hydrogels were determined by rheology, pointing out a decrease of the elastic modulus (G') with the length of the EG segment. To enhance the stability of the hydrogels after swelling, the EGnSA monomers were copolymerized with a polar monomer, 2-hydroxyethyl acrylate (HEA), leading to P[(EGnSA)x-co-HEAy] with improved compatibility in aqueous media, making it a less brittle material. Swelling properties of the hydrogels increased in the presence of hydrogen peroxide, a kind of ROS, reaching values of ≈130% for P[(EG3SA)7-co-HEA93] which confirms the stimuli-responsive properties. Then, the P[(EG3SA)x-co-HEAy] hydrogels were employed as matrixes for the encapsulation of a chemotherapeutic drug, 5-fluorouracil (5FU), which showed sustained release over time modulated by the presence of H2O2. Finally, the effect of the 5-FU release from P[(EG3SA)x-co-HEAy] hydrogels was tested in vitro with melanoma cancer cells B16F10, pointing out B16F10 growth inhibition values in the range of 40-60% modulated by the EG3SA percentage and the presence or absence of ROS agents, thus confirming their excellent ROS-responsive properties for the treatment of localized pathologies.

Mussel-inspired controllable drug release hydrogel for transdermal drug delivery: Hydrogen bond and ion-dipole interactions

Hydrogels have broad application prospects in drug delivery due to their biocompatibility, high water content and three-dimensional structure. However, the regulation of drug release from hydrogels is an important issue in medical applications. At the same time, water also has an important impact on drug release. In this study, a hydrogel with hydrogen bond and ion dipole interaction (PAHDP) was prepared by introducing catechol group into polymer to regulate drug release. Ten model drugs were selected to explore the relationship and mechanism of action among polymer, drug and water. The results showed that PAHDP had excellent adhesion and safety. Drug release test showed that 10 kinds of drugs had different drug release trends, and the release amount was negatively correlated with drug polarizability and LogP. In addition, in vitro transdermal test and pharmacokinetic results showed that the hydrogel based on PAHDP achieved increased or decreased blood drug concentration, and the area under the concentration-time curve (AUC) of >1.5 times showed its potential to regulate drug release. The mechanism study showed that the hydrogen bond and ion dipole interaction between polymer and drug were affected by drug polarizability and LogP, and the distribution of water in different states was changed. Hydrogen bond and ion dipole interactions synergistically control drug release. Therefore, the mussel inspired PAHDP hydrogel has the potential to become a controllable drug delivery system.

Preparation and optimization of agarose or polyacrylamide/amino acid-based double network hydrogels for photocontrolled drug release

The high water content and biocompatibility of amino-acid-based supramolecular hydrogels have generated growing interest in drug delivery research. Nevertheless, the existing dominant approach of constructing such hydrogels, the exploitation of a single amino acid type, typically comes with several drawbacks such as weak mechanical properties and long gelation times, hindering their applications. Here, we design a near-infrared (NIR) light-responsive double network (DN) structure, containing amino acids and different synthetic or natural polymers, i.e., polyacrylamide, poly(N-isopropylacrylamide), agarose, or low-gelling agarose. The hydrogels displayed high mechanical strength and high drug-loading capacity. Adjusting the ratio of Fmoc-Tyr-OH/Fmoc-Tyr(Bzl)-OH or Fmoc-Phe-OH/Fmoc-Tyr(Bzl)-OH, we could drastically shorten the gelation time of the DN hydrogels at room and body temperatures. Moreover, introducing photothermal agents (graphene oxide, carbon nanotubes, molybdenum disulfide nanosheets, or indocyanine green), we equipped the hydrogels with NIR responsivity. We demonstrated the light-triggered release of the drug baclofen, which is used in severe spasticity treatment. Rheology and stability tests confirmed the positive impact of the polymers on the mechanical strength of the hydrogels, while maintaining good stability under physiological conditions. Overall, our study contributed a novel hydrogel formulation with high mechanical resistance, rapid gel formation, and efficient NIR-controlled drug release, offering new opportunities for biomedical applications.

A novel adhesive dual-sensitive hydrogel for sustained release of exosomes derived from M2 macrophages promotes repair of bone defects

The repair of bone defects remains a huge clinical challenge. M2 macrophage-derived exosomes (M2-Exos) can act as immunomodulators to promote fracture healing; however, how to retain the sustained release of exosomes to the target area remains a challenge. Here, we report a composite hydrogel loaded with M2-Exos aiming to accelerate bone defect healing. It was verified that the F127/HA-NB hydrogel had a dense network structure, tissue adhesiveness, and dual sensitivity to temperature and light. F127/HA-NB loaded with M2-Exos (M2-Exos@F127/HA-NB) exhibited good biocompatibility and achieved sustained release of exosomes for up to two weeks. The study showed that both M0-Exos and M2-Exos@F127/HA-NB significantly promoted osteogenic differentiation of rat bone marrow mesenchymal stem cells. The mechanism study implied that M2-Exos activates the Wnt/β-catenin signaling pathway to promote osteogenic differentiation of BMSCs. Finally, we evaluated the osteogenetic effects of M2-Exos@F127/HA-NB in a rat cranial defect model, and the results showed that M2-Exos@F127/HA-NB had superior bone regeneration-promoting effects. This study provides a new strategy for cell-free treatment of bone defects.

Pluronic F-127 Hydrogel Loaded with Human Adipose-Derived Stem Cell-Derived Exosomes Improve Fat Graft Survival via HIF-1α-Mediated Enhancement of Angiogenesis.

Autologous fat grafting is playing an increasingly important role in plastic surgery. However, high absorption and low survival of autologous fat grafts limit their clinical application. This study aimed to investigate whether human adipose-derived stem cell-derived exosomes (hASC-Exos) encapsulated in a PF-127 hydrogel can improve the survival of autologous fat grafts and to elucidate the underlying mechanisms. Exosomes were isolated from hASCs and identified using transmission electron microscopy, nanoparticle tracking analysis and Western blotting. We performed functional assays in vitro to assess the effect of hASC-Exos on proliferation, migration, and tube formation as well as their regulatory role in the HIF-1α/VEGF signaling pathway. hASC-Exos encapsulated in the PF-127 hydrogel were used as an in vivo autologous fat graft model. The effects of the PF-127 hydrogel/hASC-Exos and the role of the HIF-1α/VEGF signaling pathway in promoting angiogenesis in an autologous fat grafting model were assessed. hASC-Exos were taken up by human umbilical vein endothelial cells and enhanced their proliferation, migration, and tubule formation in vitro. The effects of hASC-Exos on promoting angiogenesis were mediated by the HIF-1α/VEGF signaling pathway. Moreover, we fabricated a PF-127 hydrogel for the sustained release of hASC-Exos, and in vivo results showed that hASC-Exos encapsulated in PF-127 hydrogel improved the survival of autologous fat grafts. Our findings indicated that hASC-Exos encapsulated in PF-127 hydrogel serve as a key regulator of angiogenesis by activating the HIF-1α/VEGF signaling pathway and provide a promising strategy for autologous fat grafting treatment.

Bacteria-responsive hydrogel for on-demand release of antimicrobial peptides that prevent superbug infections and promote wound healing

Various skin infections present a substantial challenge in both patient care and the medical community. A primary obstacle to effective wound healing is the colonization of pathogenic bacteria, which would produce hyaluronidase (HAase). This enzyme degrades hyaluronic acid (HA) at wound sites, facilitating bacterial infection. Herein, we developed a HAase-responsive hydrogel, HA-EPL-PEG, incorporating the antimicrobial peptide ε-Poly-l-lysine (EPL) and Polyethylene glycol diacrylate (PEGDA), chemically crosslinked via a photoinitiator. Following, the in vitro antibacterial and antifouling properties of this hydrogel were evaluated, along with its cytotoxicity to mammalian cells. Subsequently, its bacteria secreted HAase responsive functionality was evaluated. In vivo antibacterial, anti-infectious and wound healing effects were further investigated in a rodent model. All these results demonstrated the multifunctional benefits of HA-EPL-PEG hydrogel, showcasing its HAase-responsive nature, antibacterial and antifouling activities. Importantly, the hydrogel significantly expedited the healing of full-thickness skin wounds, denoting a promising avenue for advancing wound care.

ApoSEVs-Mediated Modulation of Versatile Target Cells Promotes Diabetic Wound Healing: Unveiling a Promising Strategy.

Diabetic chronic wounds present a formidable challenge in clinical management, lacking effective treatment options. Mesenchymal stem cell (MSC) transplantation has emerged as a promising therapy for tissue repair and regeneration. However, transplanted MSCs often undergo rapid apoptosis, giving rise to heterogeneous extracellular vesicles (EVs), including apoptotic bodies (apoBDs) and apoptotic small extracellular vesicles (apoSEVs). The potential stimulatory role of these EVs in diabetic wound healing remains unknown. In this study, we investigated the effects of apoSEVs derived from adipose-derived mesenchymal/stromal cells (ADSCs) on the recovery of diabetic wounds by modulating the function of versatile target cells. First, we characterized the apoSEVs and apoBDs derived from apoptotic ADSCs. Subsequently, we evaluated the effects of apoSEVs and apoBDs on macrophages, endothelial cells, and fibroblasts, three essential cell types in wound healing, under high-glucose conditions. Furthermore, we developed a gelatin methacryloyl (GelMA) hydrogel for the sustained release of apoSEVs and investigated its therapeutic effects on wound healing in type 2 diabetic mice in vivo. apoSEVs facilitated the polarization of M1 phenotype macrophages to M2 phenotype, promoted proliferation, migration, and tube formation of endothelial cells, and enhanced fibroblast proliferation and migration. However, apoBDs failed to improve the function of endothelial cells and fibroblasts. In vivo, the apoSEVs-loaded GelMA effectively promoted wound healing by facilitating collagen fiber deposition, angiogenesis, and immune regulation. Our study elucidates the beneficial effects of apoSEVs on wound recovery in diabetes and introduces a novel strategy for diabetic wound treatment based on apoSEVs.

Mangiferin loaded carrageenan/chitosan core-shell hydrogel beads: Preparation, characterization and proposed application

In this work, an investigation on the use of mangiferin, a bioactive compound, in a controlled release hydrogel system was carried out. Mangiferin isolated from mango leave waste was tested for its antibacterial activities by disc diffusion, agar well and agar dilution methods. The results confirmed effective antibacterial effects against Vibrio parahaemolyticus and Vibrio cholerae, the common species found in fresh seafood that can cause acute diarrheal illness. However, application of this polyphenolic natural compound is limited by its poor water solubility resulting in low bioavailability. To overcome is limitation, biopolymeric core-shell hydrogel beads incorporated with mangiferin were fabricated by a one-step gelling method. The core particles loaded with mangiferin were prepared from κ-carrageenan solution which were subsequently ionic-crosslinked and encapsulated with the chitosan shells. The formation of core-shell morphology was verified by light microscope observation and confirmed that the κ-carrageenan core was completely covered with the uniform shell of chitosan. The composition of microsphere beads was also examined with Fourier transform infrared spectroscopy and scanning electron microscopy equipped with energy dispersive X-ray analysis. The core-shell hydrogel was able to encapsulate mangiferin with the optimum loading efficiency of 85%. The release kinetics was evaluated at different temperatures and Korsmeyer-Peppas was the most appropriate model to represent the release profiles of mangiferin from hydrogel beads. Biocompatibility test performed on all of the hydrogel samples exhibited a good viability for the L929 and Vero cells with low cytotoxicity. Investigations on the microsphere hydrogels revealed that they could regulate the release of bioactive mangiferin and possessed promising potential to be utilized for quality protection of fresh seafood.

Preparation and antibacterial activity of chitosan grafted cyclodextrin hydrogel loaded berberine hydrochloride using dual gelling agent

In this paper, cyclodextrin-grafted-chitosan (CD-g-CS) with different degrees of substitution (DS) was synthesized successfully by the reaction of O-p-toluenesulfonyl-β-cyclodextrin (TCD) and chitosan (CS), and a novel injectable thermosensitive hydrogel with rapid gelation was developed by physical cross-linking using dual gelling agents of αβ-glycerophosphate-sodium and hydrogen carbonate (GP-SHC). The results of 1H-NMR showed that the DS of CD-g-CS increased with the increase of TCD/CS (w/w). The influence of CD-g-CS with different DS, the concentration of SHC, and the ratio of CD-g-CS/GP-SHC (v/v) on gel time, swelling, drug release, degradation, and antibacterial activity of hydrogels prepared were studied. The results of FTIR indicated that the intermolecular interaction occurred in the hydrogel. And the hydrogel had a three-dimensional porous structure seen from SEM images. Compared with CS/GP hydrogel, the gel time of prepared hydrogel was shorter, which was less than 6 min, and the shortest gel time was 0.5 min. The prepared hydrogels had a good swelling ratio and degradable behavior. Berberine hydrochloride (BBH) was used as a model drug, and the gel showed a sustained drug release profile. In addition, the hydrogel had excellent antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Therefore the BBH@CD-g-CS/GP-SHC hydrogels had great potential in the development of biomedical drug delivery systems and antibacterial materials.