Chitosan-based hydrogels: From preparation to applications, a review.

Chitosan, derived from the deacetylation of chitin, is an abundant natural biopolymer on earth. Chitosan and its derivatives have become promising biological materials because of their unique molecular structure and excellent biological activities. The reactive functional groups of chitosan such as the amino and hydroxyl groups play a crucial role in facilitating the synthesis of three-dimensional hydrogel. Chitosan-based hydrogels have been widely used in medical, pharmaceutical, and environmental fields for years. Nowadays, chitosan-based hydrogels have been found in a wide range of applications in the food industry such as food sensors, dye adsorbents and nutrient carriers. In this review, recently developed methods for the preparation of chitosan-based hydrogels were given, and the biological activities of chitosan-based hydrogels were systematically introduced. Additionally, the recent progress in food sensors, packaging, dye adsorbents, and nutrient carriers was discussed. Finally, the challenges and prospects for the future development of chitosan-based hydrogels were discussed.

Multifunctional chitosan-based hydrogel wound dressing loaded with Acanthopanax senticosus and Osmundastrum cinnamomeum: Preparation, characterization and coagulation mechanism.

Considerable potential exists for the development of natural polymer hydrogels that possess notable antibacterial and anti-inflammatory properties, along with excellent biocompatibility and mechanical attributes, to expedite the healing of skin wounds. Recent endeavors have focused on formulating an optimal hydrogel dressing for wound hemostasis and repair. In this pursuit, we have crafted a composite hydrogel using carboxymethyl chitosan and alginic acid, cross-linked with EDC/NHS, and enriched with extracts from Acanthopanax senticosus and Osmundastrum cinnamomeum. This synthesized hydrogel showcases commendable features, including significant swelling capacity (135 ± 3.6%), proficient water retention (94.421 ± 0.154%), and effective water vapor permeability (5845.011 ± 467.799 g/m2/d). Moreover, our drug-loaded hydrogels (CMCS/SA/AS/OC) have demonstrated remarkable efficacy in accelerating wound healing in both in vivo and in vitro models. On the 7th day, the wound healing rate reached 94.905% ± 0.498%, and by the 14th day, the wound was nearly fully healed (98.08% ± 0.323%) with the emergence of hair coverage. Furthermore, these hydrogels exhibited remarkable hemostatic properties, the platelet activity was 89.37% ± 1.29% and the platelet adhesion rate was 66.36% ± 1.42%. In order to elucidate the coagulation mechanism of the Acanthopanax senticosus and Osmundastrum cinnamomeum extracts, a network pharmacology approach was carried out. 41 active compounds and 107 potential therapeutic targets associated with these extracts were identified, revealing a total of 132 coagulation pathways. Platelet activation and complement and coagulation cascades pathways showed the highest levels of enrichment by KEGG analysis, serving as potential mechanisms through which the active components in AS/OC may facilitate coagulation by targeting relevant factors. In summary, our study has successfully developed an innovative drug-loaded hydrogel that not only enhances wound hemostasis and healing but also provides insights into the underlying mechanisms through network pharmacology. This work establishes a robust theoretical foundation for the medical application of our hydrogel.

Chitosan-based hydrogel wound dressing: From mechanism to applications, a review.

As promising biomaterials, hydrogels are widely used in the medical engineering field, especially in wound repairing. Compared with traditional wound dressings, such as gauze and bandage, hydrogel could absorb and retain more water without dissolving or losing its three-dimensional structure, thus avoiding secondary injury and promoting wound healing. Chitosan and its derivatives have become hot research topics for hydrogel wound dressing production due to their unique molecular structure and diverse biological activities. In this review, the mechanism of wound healing was introduced systematically. The mechanism of action of chitosan in the first three stages of wound repair (hemostasis, antimicrobial properties and progranulation), the effect of chitosan deacetylation and the molecular weight on its performance are analyzed. Additionally, the recent progress in intelligent and drug-loaded chitosan-based hydrogels and the features and advantages of chitosan were discussed. Finally, the challenges and prospects for the future development of chitosan-based hydrogels were discussed.

Preparation of chitosan/Enoki mushroom foot polysaccharide composite cling film and its application in blueberry preservation.

In this study, the composite cling film was prepared by solution casting method using chitosan and golden mushroom foot polysaccharide as substrates, and the structure and physicochemical indexes of the composite cling film were characterized by Fourier infrared spectroscopy, X-ray diffraction, and scanning electron microscopy. The results showed that compared with single chitosan film, the composite cling film has better mechanical properties and antioxidant properties, and the barrier of UV light and water vapor is also stronger. Due to its high nutritional value, blueberry has a short shelf life due to its thin skin and poor storage resistance. Therefore, in this study, blueberry was used as the object of freshness preservation, and the single chitosan film group and the uncovered group were used as controls, and the weight loss, total bacterial colony, decay rate, respiration intensity, malondialdehyde content, hardness, soluble solids, titratable acid, anthocyanin content, and VC content of blueberry were used as freshness preservation indexes for experiments. The comprehensive results showed that the freshness preservation effect of the composite film group was significantly higher than that of the control group, with better antibacterial properties, antioxidant properties, etc., which could effectively delay fruit decay and deterioration, thus prolonging the shelf life, and thus the chitosan/Enoki mushroom foot polysaccharide composite preservation film has a high potential as a new freshness preservation material for blueberry.

Preparation of Chitosan/ß-Cyclodextrin Composite Membrane and Its Adsorption Mechanism for Proteins.

A significant portion of the protein in food waste will contaminate the water. The chitosan/modified ß-cyclodextrin (CS/ß-CDP) composite membranes were prepared for the adsorption of bovine serum albumin (BSA) in this work to solve the problem of poor adsorption protein performance and easy disintegration by a pure chitosan membrane. A thorough investigation was conducted into the effects of the preparation conditions (the mass ratio of CS and ß-CDP, preparation temperature, and glutaraldehyde addition) and adsorption conditions (temperature and pH) on the created CS/ß-CDP composite membrane. The physical and chemical properties of pure CS membrane and CS/ß-CDP composite membrane were investigated. The results showed that CS/ß-CDP composite membrane has better tensile strength, elongation at break, Young's modulus, contact angle properties, and lower swelling degree. The physicochemical and morphological attributes of composite membranes before and after the adsorption of BSA were characterized by SEM, FT-IR, and XRD. The results showed that the CS/ß-CDP composite membrane adsorbed BSA by both physical and chemical mechanisms, and the adsorption isotherm, kinetics, and thermodynamic experiments further confirmed its adsorption mechanism. As a result, the CS/ß-CDP composite membrane of absorbing BSA was successfully fabricated, demonstrating the potential application prospect in environmental protection.

Dual crosslinking of folic acid-modified pectin nanoparticles for enhanced oral insulin delivery.

Pectin-based drug delivery systems hold great potential for oral insulin delivery, since they possess excellent gelling property, good mucoadhesion and high stability in the gastrointestinal (GI) tract. However, lack of enterocyte targeting ability and premature drug release in the upper GI tract of the susceptible ionic-crosslinked pectin matrices are two major problems to be solved. To address these issues, we developed folic acid (FA)-modified pectin nanoparticles (INS/DFAN) as insulin delivery vehicles by a dual-crosslinking method using calcium ions and adipic dihydrazide (ADH) as crosslinkers. In vitro studies indicated insulin release behaviors of INS/DFAN depended on COOH/ADH molar ratio in the dual-crosslinking process. INS/DFAN effectively prevented premature insulin release in simulated GI fluids compared to ionic-crosslinked nanoparticles (INS/FAN). At an optimized COOH/ADH molar ratio, INS/DFAN with FA graft ratio of 18.2% exhibited a relatively small particle size, high encapsulation efficiency and excellent stability. Cellular uptake of INS/DFAN was FA graft ratio dependent when it was at/below 18.2%. Uptake mechanism and intestinal distribution studies demonstrated the enhanced insulin transepithelial transport by INS/DFAN via FA carrier-mediated transport pathway. In vivo studies revealed that orally-administered INS/DFAN produced a significant reduction in blood glucose levels and further improved insulin bioavailability in type I diabetic rats compared to INS/FAN. Taken together, the combination of dual crosslinking and FA modification is an effective strategy to develop pectin nano-vehicles for enhanced oral insulin delivery.

Chitosan-Based Materials: An Overview of Potential Applications in Food Packaging.

Chitosan is a multifunctional biopolymer that is widely used in the food and medical fields because of its good antibacterial, antioxidant, and enzyme inhibiting activity and its degradability. The biological activity of chitosan as a new food preservation material has gradually become a hot research topic. This paper reviews recent research on the bioactive mechanism of chitosan and introduces strategies for modifying and applying chitosan for food preservation and different preservation techniques to explore the potential application value of active chitosan-based food packaging. Finally, issues and perspectives on the role of chitosan in enhancing the freshness of food products are presented to provide a theoretical basis and scientific reference for subsequent research.

Antiarrhythmic effects of ginsenoside Rg2 on calcium chloride-induced arrhythmias without oral toxicity.

BACKGROUND: Malignant arrhythmias require drug therapy. However, most of the currently available antiarrhythmic drugs have significant side effects. Ginsenoside Rg2 exhibits excellent cardioprotective effects and appears to be a promising candidate for cardiovascular drug development. So far, the oral toxicity and antiarrhythmic effects of Rg2 have not been evaluated. METHODS: Acute oral toxicity of Rg2 was assessed by the Limit Test method in mice. Subchronic oral toxicity was determined by repeated dose 28-day toxicity study in rats. Antiarrhythmic activities of Rg2 were evaluated in calcium chloride-induced arrhythmic rats. Antiarrhythmic mechanism of Rg2 was investigated in arrhythmic rats and H9c2 cardiomyocytes. RESULTS: The results of toxicity studies indicated that Rg2 exhibited no single-dose (10 g/kg) acute oral toxicity. And 28-day repeated dose treatment with Rg2 (1.75, 3.5 and 5 g/kg/d) demonstrated minimal, if any, subchronic toxicity. Serum biochemical examination showed that total cholesterol in the high-dose cohort was dramatically decreased, whereas prothrombin time was increased at Day 28, suggesting that Rg2 might regulate lipid metabolism and have a potential anticoagulant effect. Moreover, pretreatment with Rg2 showed antiarrhythmic effects on the rat model of calcium chloride induced arrhythmia, in terms of the reduced duration time, mortality, and incidence of malignant arrhythmias. The antiarrhythmic mechanism of Rg2 might be the inhibition of calcium influx through L-type calcium channels by suppressing the phosphorylation of Ca2+/calmodulin-dependent protein kinase II. CONCLUSION: Our findings support the development of Rg2 as a promising antiarrhythmic drug with fewer side effects for clinical use.

Polylactide nanofibers delivering doxycycline for chronic wound treatment.

Chronic wounds are of high incidence, difficult to heal, and can cause serious consequences if not properly treated. Doxycycline (DCH) is a broad-spectrum antibiotic and matrix metalloproteinases inhibitor, which has prominent efficacy for chronic wound treatment. Topical DCH treatment is the common administration route for chronic wounds in clinic but may result in low therapeutic efficacy and cause skin irritation at high DCH concentration, since it is difficult to control local drug concentration in the wounds and maintain the effective DCH concentration for a long time. In this study, we prepared DCH-encapsulated polylactide (DCH/PLA) nanofibers by a simple electrospinning method. Imaging studies showed that smooth and continuous DCH/PLA nanofibers with homogeneous DCH distribution were obtained at varied DCH loading content in the range of 5-30%. Mechanical property, water vapour permeability and absorbency of these nanofibers could meet the requirement as wound dressings. By adjusting DCH loading content, the wettability of the nanofibers could be transferred from hydrophobic to hydrophilic, and the release rate of DCH could be controlled in a sustained manner from three days to two weeks. Results of cytotoxicity and antibacterial test indicated that DCH/PLA nanofibers showed good cytocompatibility to L929 mouse fibroblast cells and exhibited positive antibacterial activity against Escherichia coli, suggesting its ability to treat/prevent infectious wounds. For full-thickness wound treatment of diabetic rats, DCH/PLA nanofiber mats can speed up wound healing to a higher extent than topical DCH treatment, due to the sustained release of DCH with less side effects. Our results indicate that DCH/PLA nanofiber mats hold great potential as wound dressings for chronic wound treatment.

Ginsenoside Rg2 protects PC12 cells against ß-amyloid25-35-induced apoptosis via the phosphoinositide 3-kinase/Akt pathway.

Alzheimer's disease (AD) is one of the most debilitating neurodegenerative diseases in an aging population. Excessive accumulation of ß-amyloid (Aß) has been proposed as a pivotal event in the pathogenesis of AD. Ginsenoside Rg2 has been reported to exert neuroprotective effects. However, the underlying mechanism for its neuroprotection is not well-understood. In this study, we investigated the protective effects of ginsenoside Rg2 on Aß25-35-induced neurotoxicity in PC12 cells and identified a potential molecular signaling pathway involved. The results showed that pretreatment of PC12 cells with ginsenoside Rg2 followed by Aß25-35 increased cell viability in a concentration-dependent manner compared to cells that were not pretreated. In addition, ginsenoside Rg2 pretreatment attenuated Aß25-35-induced increases in the release of lactate dehydrogenase, the intracellular calcium concentration, and levels of reactive oxygen species. Pretreatment with ginsenoside Rg2 increased the Bcl-2/Bax ratio. Moreover, ginsenoside Rg2 attenuated the cleavage of caspase-3 induced by Aß25-35 thereby improving cell survival. Ginsenoside Rg2 significantly enhanced the phosphorylation of Akt in PC12 cells. Additionally, pretreatment with the phosphoinositide 3-kinase (PI3K) inhibitor, LY294002, completely abolished the protective effects of ginsenoside Rg2 against Aß25-35-induced neuronal cell apoptosis. These findings unambiguously suggested that the protective effect of ginsenoside Rg2 against Aß25-35-induced apoptosis in PC12 cells was associated with enhancement of the PI3K/Akt signaling pathway.

Effects of pectin structure and crosslinking method on the properties of crosslinked pectin nanofibers.

We reported crosslinking of electrospun nanofibers of three representative pectins (high-methoxylated, low-methoxylated, low-methoxylated and amidated pectin) and characterization of the crosslinked nanofibers. One mono-crosslinking strategy and two dual-crosslinking strategies were developed. Mono-crosslinking is achieved using calcium ions (Ca2+) to crosslink carboxylate ions in galacturonic acid residues. Dual-crosslinking is achieved using covalent crosslinking reagents glutaraldehyde (GLU) or adipic acid dihydrazide (ADH) to further crosslink hydroxyl groups or carboxylate ions after Ca2+ crosslinking. Mechanical tests and degradation experiments indicated pectin structure affected mechanical and degradation properties of Ca2+-crosslinked nanofibers remarkably. Subsequent GLU crosslinking improved their mechanical strength moderately but did not inhibit their degradation, while subsequent ADH crosslinking improved their mechanical strength and slowed down their degradation dramatically. Cell studies demonstrated that most crosslinked pectin nanofibers were of no obvious cytotoxicity, and both ADH crosslinking and high degree of methoxylation facilitated cell adhesion and proliferation on pectin nanofiber mats.

Protective effects of ginsenoside Rg2 against H2O2-induced injury and apoptosis in H9c2 cells.

Ginsenoside Rg2 is one of the major active components of ginseng and has many biological activities. This study aimed to investigate the protective effects of ginsenoside Rg2 against H2O2-induced injury and apoptosis in H9c2 cells. The results showed that pretreatment with ginsenoside Rg2 not only increased cell viability, but also decreased lactate dehydrogenase (LDH) release. Ginsenoside Rg2 inhibited the decrease of SOD, GSH-PX activities and the increase of MDA content induced by H2O2. Meanwhile, the levels of ROS generation and cardiomyocyte apoptosis in ginsenoside Rg2 group significantly reduced when compared with the model group. Western blot analyses demonstrated that ginsenoside Rg2 up-regulate level of Bcl-2 expression and down-regulate levels of Bax, Caspase-3, -9 expression. These findings indicated that ginsenoside Rg2 could protect H9c2 cells against H2O2-induced injury through its actions of anti-oxidant and anti-apoptosis.

Efficient biotransformation of polysialogangliosides for preparation of GM1 by Cellulosimicrobium sp. 21.

A new ganglioside transformed strain isolated from soil was identified as Cellulosimicrobium sp. 21. It produced a sialidase which transformed polysialo-gangliosides GD1 and GT1 into a monosialoterahexosylganglioside, i.e., ganglioside GM1. The sialidase had both NeuAc-α-2,3- and NeuAc-α-2,8-sialidase activity without producing asiolo-GM1. The optimum conditions were evaluated and it was found that the transformation was optimally performed at 30 °C and pH 7.0. The substrate should be added at the beginning of the reaction and the concentration of substrate was 3% (w/v). Under these optimum conditions, Cellulosimicrobium sp. 21 converted GD1 and GT1 into GM1 in inorganic medium in a 5 L bioreactor with the recovery rate of 69.3%. The product contained 50.3% GM1 and was purified on silica to give the product with 95% of GM1 with a recovery rate of 30.5%. Therefore, Cellulosimicrobium sp. 21 has potential to be applied in the production of GM1 in the pharmaceutical industry.