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.

Metformin-Loaded Chitosan Hydrogels Suppress Bladder Tumor Growth in an Orthotopic Mouse Model via Intravesical Administration.

Our previous study found that the intravesical perfusion of metformin has excellent inhibitory effects against bladder cancer (BC). However, this administration route allows the drug to be diluted and excreted in urine. Therefore, increasing the adhesion of metformin to the bladder mucosal layer may prolong the retention time and increase the pharmacological activity. It is well known that chitosan (Cs) has a strong adhesion to the bladder mucosal layer. Thus, this study established a novel formulation of metformin to enhance its antitumor activity by extending its retention time. In this research, we prepared Cs freeze-dried powder and investigated the effect of metformin-loaded chitosan hydrogels (MLCH) in vitro and in vivo. The results showed that MLCH had a strong inhibitory effect against proliferation and colony formation in vitro. The reduction in BC weight and the expression of tumor biomarkers in orthotopic mice showed the robust antitumor activity of MLCH via intravesical administration in vivo. The non-toxic profile of MLCH was observed as well, using histological examinations. Mechanistically, MLCH showed stronger functional activation of the AMPKα/mTOR signaling pathway compared with metformin alone. These findings aim to make this novel formulation an efficient candidate for managing BC via intravesical administration.

Influence of Glycerophosphate Salt Solubility on the Gelation Mechanism of Colloidal Chitosan Systems.

Recently, thermosensitive chitosan systems have attracted the interest of many researchers due to their growing application potential. Nevertheless, the mechanism of the sol-gel phase transition is still being discussed, and the glycerophosphate salt role is ambiguous. The aim of the work is to analyze the possibility of the exclusive use of a non-sodium glycerophosphate salt and to determine its impact on the gelation conditions determined by rheological and turbidimetric measurements as well as the stability of the systems by measuring changes in the Zeta potential value. It was found that ensuring the same proportions of glycerophosphate ions differing in cation to amino groups present in chitosan chains, leads to obtaining systems significantly different in viscoelastic properties and phase transition conditions. It was clearly shown that the systems with the calcium glycerophosphate, the insoluble form of which may constitute additional aggregation nuclei, undergo the gelation the fastest. The use of magnesium glycerophosphate salt delays the gelation due to the heat-induced dissolution of the salt. Thus, it was unequivocally demonstrated that the formulation of the gelation mechanism of thermosensitive chitosan systems based solely on the concentration of glycerophosphate without discussing its type is incorrect.

Composite chitosan hydrogels as advanced wound dressings with sustained ibuprofen release and suitable application characteristics.

The physical chitosan hydrogel, obtained by ionic gelation in lactic acid solution, was combined with biocompatible oil-in-water microemulsion with ibuprofen, to prepare composite hydrogels with 0.25-1% of the polymer and 5% of the drug. The electrical conductivity measurement, photon correlation spectroscopy (PCS), and rheological analysis showed that the composite hydrogels comprise oil nanodroplets (16.21-22.56 nm) embedded within pseudoplastic chitosan hydrogel. In vitro ibuprofen release was sustained for 12 h and followed zero-order kinetics. pH values of the composite hydrogels were in the range of 4.80-5.27, thus physiologically acceptable. The formulation containing 0.5% chitosan enabled the maximum drug release rate of 239.25 µgh-1cm-2 as well as cohesiveness (154.958 ± 0.731 g*s) higher than hardness (13.546 ± 0.065 g) and adhesiveness (-12.042 ± 1.161 g*s), so textural properties were suitable for application along skin surface, without spillage, and for easy removal. This is the first study in which the composite chitosan hydrogels with ibuprofen were formulated by combining the chitosan hydrogel prepared without harmful chemical crosslinkers and low viscosity oil-in-water microemulsion, and the preclinical characterization of their biopharmaceutical aspect and textural characterization, that is of key importance in improving the patient's compliance, were performed.

Chitosan hydrogels significantly limit left ventricular infarction and remodeling and preserve myocardial contractility.

BACKGROUND: Left ventricular myocardial infarctions (MIs) consist of a central area of myocardial necrosis that is surrounded by areas of myocardial injury and ischemia. We hypothesized that chitosan hydrogels, when injected around the perimeter of MIs in rats, could decrease left ventricle (LV) wall stress by the Law of LaPlace, and therefore myocardial oxygen requirements, and prevent the ischemic and injured myocardium from becoming necrotic. In this manner, chitosan gels could limit LV infraction size and LV remodeling. Chitosan hydrogels are liquid at 25°C but gel at 37°C. METHODS: Seventy Sprague-Dawley rats with ligation of the left coronary artery were treated with either Dulbecco's Modified Eagle Medium (DMEM) or chitosan hydrogel in DMEM, which was injected around the infarct perimeter. Echocardiograms were obtained before MI and at 2, 4, 8, 12, and 16 wk after MI. Hearts from randomly selected rats were harvested at baseline and at the time of echocardiography for determinations of LV infarct size, remodeling, and histopathology. RESULTS: Infarct sizes as a percentage of the total ventricular myocardium in the DMEM group averaged 17% versus 14% in the chitosan group at 4 wk (P < 0.05), 18% versus 14% at 8 wk (P < 0.01), 19% versus 14% at 12 wk (P < 0.001), and 20% versus 14% at 16 wk (P < 0.001). Injection of chitosan into the infarctions produced LV wall thicknesses in the MI border zones that averaged 0.66 cm at 4 wk, which were greater than the LV wall thicknesses in the border zones of rats treated with DMEM, which averaged 0.33 cm (P < 0.01). Arteriole densities in the MI border zones were 160/mm(2) in the chitosan group but only 92/mm(2) in the DMEM rats (P < 0.01). The left ventricular end-diastolic diameters (LVEDs) in the rats averaged 0.73 cm before MI. After MI, LVED increased in the DMEM rats to 0.84 cm at 2 wk, then 0.89 cm at 4 wk, 0.89 cm at 8 wk, 0.89 m at 12 wk, and 0.87 cm at 16 wk. In contrast, LVED in the chitosan rats were on average 19% smaller in comparison with the DMEM rats (P < 0.05) and did not significantly change in comparison with their baseline LVEDs. Left ventricular ejection fraction (LVEF) in the rats averaged 83% before infarctions. In the infarction + DMEM group, the LVEFs significantly decreased after MI and averaged 59.7% at 2 wk, 52.5% at 4 wk, 46.1% at 8 wk, 52.4% at 12 wk, and 53.6% at 16 wk (P < 0.05). In the infarction + chitosan-treated rats, the LVEFs were greater and averaged 67.8% at 2 wk (P < 0.02), 68.9% (P < 0.02) at 4 wk, 69% (P < 0.003) at 8 wk, 65.2% at 12 wk (P < 0.05), and 67% at 16 wk (P < 0.05). CONCLUSIONS: Chitosan gel can increase LV myocardial wall thickness, decrease infarct size and LV remodeling, and preserve LV contractility.

Autonomously Sensing Hydrogels for the Rapid and Selective Detection of Pathogenic Bacteria.

The development of a versatile approach for the rapid and sensitive detection of relevant pathogenic bacteria and autonomous signaling of the detection events in reporter hydrogel film coatings is reported. Exploiting chitosan hydrogel films equipped with chromogenic or fluorogenic reporter moieties, the presence of the Gram-negative bacterium Pseudomonas aeruginosa and the Gram-positive bacterium Staphylococcus aureus is sensed within 1 h by detecting the characteristic enzymes α-glucosidase and elastase with limits of detection (LOD) <45 × 10(-9) M and <20 × 10(-9) M, respectively, for this observation time. The values for the LOD are two to three orders of magnitude smaller than the concentrations of the enzymes detected in the corresponding bacterial supernatants. The results show that the covalently conjugated reporter moieties are exclusively and efficiently reacted by the associated enzyme, allowing in principle for discrimination among different types of bacteria. Since high enzyme concentrations are a result of proliferating bacteria, e.g., in wounds or food, and since the selectivity of the reporting function is easily adapted to bacteria of choice, these reporter hydrogels comprise an interesting platform for the rapid detection of bacteria.

Ammonia-responsive chitosan/polymethacrylamide double network hydrogels with high-stretchability, fatigue resistance and anti-freezing for real-time chicken breast spoilage monitoring.

Hydrogels are a promising option for detecting food spoilage in humid conditions, but current indicators are prone to mechanical flaws, posing a concern for packaging systems that require strong mechanical properties. Herein, a double network hydrogel was prepared by polymerizing methacrylamide in a chitosan system with aluminum chloride and glycerol. The resulting hydrogel demonstrated high stretchability (strain >1500 %), notch insensitivity, excellent fatigue resistance, and exceptional anti-freezing capabilities even at -21 °C. When incorporating bromothymol blue (BB) or methyl red (MR), or mixtures of these dyes into the hydrogels as indicators, they exhibited sensitive colorimetric responses to pH and NH3 levels at different temperatures. Hydrogels immobilizing BB to MR ratios of 1:1 and 1:2 displayed clearer and more sensitive color responses when packed into chicken breast, with a sensitivity level of 1.5 ppm of total volatile basic nitrogen (TVB-N). This color response correlated positively with the accumulation of TVB-N on the packaging during storage at both 25 °C and 4 °C, providing sensitive indications of chicken breast deterioration. Overall, the developed hydrogels and indicators demonstrate enhanced performance characteristics, including excellent mechanical strength and highly NH3-sensitive color responses, making significant contributions to the food spoilage detection and intelligent packaging systems field.

Dual Chemotherapeutic Loading in Oxalate Transferrin-Conjugated Polymersomes Incorporated into Chitosan Hydrogels for Site-Specific Targeting of Melanoma Cells.

In this work, we developed a smart drug delivery system composed of poly (ethylene glycol)-block-poly (ε-caprolactone) (PEG-PCL)-based polymersomes (Ps) loaded with doxorubicin (DOX) and vemurafenib (VEM). To enhance targeted delivery to malignant melanoma cells, these drug-loaded nanovesicles were conjugated to the oxalate transferrin variant (oxalate Tf) and incorporated into three-dimensional chitosan hydrogels. This innovative approach represents the first application of oxalate Tf for the precision delivery of drug-loaded polymersomes within a semi-solid dosage form based on chitosan hydrogels. These resulting semi-solids exhibited a sustained release profile for both encapsulated drugs. To evaluate their potency, we compared the cytotoxicity of native Tf-Ps with oxalate Tf-Ps. Notably, the oxalate Tf-Ps demonstrated a 3-fold decrease in cell viability against melanoma cells compared to normal cells and were 1.6-fold more potent than native Tf-Ps, indicating the greater potency of this nanoformulation. These findings suggest that dual-drug delivery using an oxalate-Tf-targeting ligand significantly enhances the drug delivery efficiency of Tf-conjugated nanovesicles and offers a promising strategy to overcome the challenge of multidrug resistance in melanoma therapy.

Rational design of a Nano-Antibiotic chitosan hydrogel for the bacterial infection Therapy: In vitro & ex vivo Assessments.

In modern times, many antibiotics have become less effective as microorganisms develop resistance. Besides antibiotic resistance, another bacterial strategy that contributes to the capacity to withstand antimicrobials is biofilm formation. Because of these bacterial survival strategies, the desired response cannot be achieved with conventional treatment. Considering the limited discovery of new compounds, the most logical approach is to reconstruct existing antimicrobial molecules with nano-drug delivery systems. With this scientific approach, the aim of the study is to develop a novel nano-antibiotic hydrogel formulation containing silver nanoparticles, chitosan, and amoxicillin. Endodontic disease was used as a model of biofilm-mediated infection, and the antibacterial activity of nano-antibiotic hydrogel was evaluated with the E. faecalis standard bacterial strain. By adopting the Box-Behnken design for the optimisation of formulation variables, an innovative pharmaceutical formulation with antimicrobial and antibiofilm activity was successfully obtained. Further characterisation studies, including nanoparticle characterisation, in vitro cytotoxicity, and ex vivo activity studies, were carried out on dental samples using the optimised formulation. All results were compared with antimicrobial agents routinely used in endodontic treatment. The findings mainly conclude that the optimised nano-antibiotic hydrogel may be an alternative antimicrobial formulation since it is non-cytotoxic and exhibits high antibiofilm activity.

Eco-Friendly Microwave Synthesis of Sodium Alginate-Chitosan Hydrogels for Effective Curcumin Delivery and Controlled Release.

In this study, we developed sodium alginate-chitosan hydrogels using a microwave-assisted synthesis method, aligning with green chemistry principles for enhanced sustainability. This eco-friendly approach minimizes chemical use and waste while boosting efficiency. A curcumin:2-hydroxypropyl-ß-cyclodextrin complex was incorporated into the hydrogels, significantly increasing the solubility and bioavailability of curcumin. Fourier Transform Infrared Spectroscopy (FTIR) analysis confirmed the structure and successful incorporation of curcumin, in both its pure and complexed forms, into the polymer matrix. Differential scanning calorimetry revealed distinct thermal transitions influenced by the hydrogel composition and physical cross-linking. Hydrogels with higher alginate content had higher swelling ratios (338%), while those with more chitosan showed the lowest swelling ratios (254%). Scanning Electron Microscopy (SEM) micrographs showed a porous structure as well as successful incorporation of curcumin or its complex. Curcumin release studies indicated varying releasing rates between its pure and complexed forms. The chitosan-dominant hydrogel exhibited the slowest release rate of pure curcumin, while the alginate-dominant hydrogel exhibited the fastest. Conversely, for curcumin from the inclusion complex, a higher chitosan proportion led to the fastest release rate, while a higher alginate proportion resulted in the slowest. This study demonstrates that the form of curcumin incorporation and gel matrix composition critically influence the release profile. Our findings offer valuable insights for designing effective curcumin delivery systems, representing a significant advancement in biodegradable and sustainable drug delivery technologies.

Development of dual-crosslinked Pluronic F127/Chitosan injectable hydrogels incorporating graphene nanosystems for breast cancer photothermal therapy and antibacterial applications.

Nanomaterials with responsiveness to near-infrared light can mediate the photoablation of cancer cells with an exceptional spatio-temporal resolution. However, the therapeutic outcome of this modality is limited by the nanostructures' poor tumor uptake. To address this bottleneck, it is appealing to develop injectable in situ forming hydrogels due to their capacity to perform a tumor-confined delivery of the nanomaterials with minimal off-target leakage. In particular, injectable in situ forming hydrogels based on Pluronic F127 have been emerging due to their FDA-approval status, biocompatibility, and thermosensitive sol-gel transition. Nevertheless, the application of Pluronic F127 hydrogels has been limited due to their fast dissociation in aqueous media. Such limitation may be addressed by combining the thermoresponsive sol-gel transition of Pluronic F127 with other polymers with crosslinking capabilities. In this work, a novel dual-crosslinked injectable in situ forming hydrogel based on Pluronic F127 (thermosensitive gelation) and Chitosan (ionotropic gelation in the presence of NaHCO3), loaded with Dopamine-reduced graphene oxide (DOPA-rGO; photothermal nanoagent), was developed for application in breast cancer photothermal therapy. The dual-crosslinked hydrogel incorporating DOPA-rGO showed a good injectability (through 21 G needles), in situ gelation capacity and cytocompatibility (viability > 73 %). As importantly, the dual-crosslinking improved the hydrogel's porosity and prevented its premature degradation. After irradiation with near-infrared light, the dual-crosslinked hydrogel incorporating DOPA-rGO produced a photothermal heating (ΔT ≈ 22 °C) that reduced the breast cancer cells' viability to just 32 %. In addition, this formulation also demonstrated a good antibacterial activity by reducing the viability of S. aureus and E. coli to 24 and 33 %, respectively. Overall, the dual-crosslinked hydrogel incorporating DOPA-rGO is a promising macroscale technology for breast cancer photothermal therapy and antimicrobial applications.

New Hydrogels Nanocomposites Based on Chitosan, 2-Formylphenylboronic Acid, and ZnO Nanoparticles as Promising Disinfectants for Duodenoscopes Reprocessing.

New hydrogels nanocomposites, based on iminoboronate hydrogels and ZnO nanoparticles (ZnO-NPs), were obtained and characterised in order to develop a new class of disinfectants able to fight the nosocomial infections produced by duodenoscopes investigation procedures. The formation of the imine linkages between chitosan and the aldehyde was demonstrated using NMR and FTIR spectroscopy, while the supramolecular architecture of the developed systems was evaluated via wide-angle X-ray diffraction and polarised optical microscopy. The morphological characterisation of the systems via scanning electron microscopy revealed the highly porous structure of the materials, in which no ZnO agglomeration could be observed, indicating the very fine and homogenous encapsulation of the nanoparticles into the hydrogels. The newly synthetised hydrogels nanocomposites was proven to have synergistic antimicrobial properties, being very efficient as disinfectants against reference strains as: Enterococcus faecalis, Klebsiella pneumoniae, and Candida albicans.

Drug delivery based on a supramolecular chemistry approach by using chitosan hydrogels.

Microbial infections are a serious healthcare related problem, causing several complications and even death. That is why, the development of new drug delivery systems with prolonged effect represents an interesting research topic. This study presents the synthesis and characterization of new hydrogels based on chitosan and three halogenated monoaldehydes. Further, the hydrogels were used as excipients for the development of drug delivery systems (DDS) by the incorporation of fluconazole, an antifungal drug. The systems were structurally characterized by Fourier Transformed Infrared Spectroscopy and Nuclear Magnetic Resonance, both methods revealing the formation of the imine linkages between chitosan and the aldehydes. The samples presented a high degree of ordering at supramolecular level, as demonstrated by WXRD and POM and a good water-uptake, reaching a maximum of 1.6 g/g. The obtained systems were biodegradable, loosing between 38 and 49 % from their initial mass in the presence of lysozyme in 21 days. The ability to release the antifungal drug in a sustained manner for seven days, along with the high values of the inhibition zone diameter, reaching a maximum of 64 mm against Candida parapsilosis for the chlorine containing sample, recommend these systems as promising materials for bioapplications.

Reinforcement of the antimicrobial activity and biofilm inhibition of novel chitosan-based hydrogels utilizing zinc oxide nanoparticles.

Two novel chemically cross-linked chitosan hydrogels were successfully prepared via insertion of oxalyl dihydrazide moieties between chitosan Schiff's base chains (OCsSB) and between chitosan chains (OCs). For more modification, two different concentrations of ZnO nanoparticles (ZnONPs) were loaded into OCs to obtain OCs/ZnONPs-1 % and OCs/ZnONPs-3 % composites. The prepared samples were recognized using elemental analyses, FTIR, XRD, SEM, EDS and TEM. Their inhibitory action against microbes and biofilms were classified as: OCs/ZnONPs-3 % > OCs/ZnONPs-1 % > OCs > OCsSB > chitosan. OCs has inhibition activity similar to Vancomycin of minimum inhibitory concentration (MIC) value of 3.9 µg/mL against P. aeruginosa. OCs exhibited minimum biofilm inhibitory concentration (MBIC) values (from 31.25 to 62.5 µg/mL) less than that of OCsSB (from 62.5 to 250 µg/mL) which lower than that of chitosan (from 500 to 1000 µg/mL) against S. epidermidis, P. aeruginosa and C. albicans. OCs/ZnNPs-3 % showed MIC value (that caused 100 % inhibition of Clostridioides difficile, C. difficile) of 0.48 µg/mL much lower than Vancomycin (1.95 µg/mL). Both OCs and OCs/ZnONPs-3 % composite were safe on normal human cells. Thus, inclusion of oxalyl dihydrazide and ZnONPs into chitosan greatly reinforced its antimicrobial activity. This is a good strategy to accomplish adequate systems for competing traditional antibiotics.

Glucose-Responsive Microgel Comprising Conventional Insulin and Curcumin-Laden Nanoparticles: a Potential Combination for Diabetes Management.

Successful management of type 2 diabetes mellitus (T2DM), a complex and chronic disease, requires a combination of anti-hyperglycemic and anti-inflammatory agents. Here, we have conceptualized and tested an integrated "closed-loop mimic" in the form of a glucose-responsive microgel (GRM) based on chitosan, comprising conventional insulin (INS) and curcumin-laden nanoparticles (nCUR) as a potential strategy for effective management of the disease. In addition to mimicking the normal, on-demand INS secretion, such delivery systems display an uninterrupted release of nCUR to combat the inflammation, oxidative stress, lipid metabolic abnormality, and endothelial dysfunction components of T2DM. Additives such as gum arabic (GA) led to a fivefold increased INS loading capacity compared to GRM without GA. The GRMs showed excellent in vitro on-demand INS release, while a constant nCUR release is observed irrespective of glucose concentrations. Thus, this study demonstrates a promising drug delivery technology that can simultaneously, and at physiological/pathophysiological relevance, deliver two drugs of distinct physicochemical attributes in the same formulation.

Advances in chitosan-based hydrogels for pharmaceutical and biomedical applications: A comprehensive review.

The treatment of diseases, such as cancer, is one of the most significant issues correlated with human beings health. Hydrogels (HGs) prepared from biocompatible and biodegradable materials, especially biopolymers, have been effectively employed for the sort of pharmaceutical and biomedical applications, including drug delivery systems, biosensors, and tissue engineering. Chitosan (CS), one of the most abundant bio-polysaccharide derived from chitin, is an efficient biomaterial in the prognosis, diagnosis, and treatment of diseases. CS-based HGs possess some potential advantages, like high values of bioactive encapsulation, efficient drug delivery to a target site, sustained drug release, good biocompatibility and biodegradability, high serum stability, non-immunogenicity, etc., which made them practical and useful for pharmaceutical and biomedical applications. In this review, we summarize recent achievements and advances associated with CS-based HGs for drug delivery, regenerative medicine, disease detection and therapy.

TiO2, CeO2, and TiO2-CeO2 nanoparticles incorporated 2.5D chitosan hydrogels: Gelation behavior and cytocompatibility.

In this study, gelation behavior and cytocompatibility of 2.5D chitosan hydrogels were investigated in the presence of TiO2, CeO2 and TiO2-CeO2 composite nanoparticles. Chemical co-precipitation method was used for nanoparticle synthesis and they were heat treated at 600 °C and 700 °C. Gelation of the chitosan solutions was carried out at 37 °C in the presence of glycerol phosphate and genipin as crosslinkers. The gelation time of chitosan was decreased by all of the nanoparticles whereas its elastic modulus was increased by nanoparticles addition. Chitosan solutions containing CeO2 or TiO2-CeO2 nanoparticles showed faster gel formation compared to chitosan solutions containing only TiO2 nanoparticles. CeO2@700 °C nanoparticles decreased the gelation time by 46% and increased elastic modulus by 14%. Average pore diameter of the hydrogel decreased from 127 ± 62 µm to 77 ± 33 µm, water uptake decreased 21% and thermal stability increased in the presence of CeO2@700 °C nanoparticles compared to chitosan hydrogel. Cell viability results indicated that chitosan hydrogels with or without nanoparticles created 2.5D environment supporting cellular proliferation approximately 1.5 times more than TCPS due to their high porous surfaces. Immunofluorescence images were also supported cell viability results. Therefore, CeO2 or TiO2-CeO2 composite nanoparticles incorporated 2.5D chitosan hydrogels may be alternative tissue engineering materials with their fast gelation, ease of use, low cost, light transparency, and cytocompatibility.

High strength chitosan hydrogels prepared from NaOH/urea aqueous solutions: the role of thermal gelling.

Upon heating and subsequent solvent displacement with pure water, the cold chitosan solution with aqueous alkaline/urea as solvent readily transforms into a hydrogel which is substantially stronger than traditional chitosan hydrogels regenerated from acidic solutions. In this work, we have systematically studied the effects of the treatment parameters in this two-step basic route and found that thermal gelation was the crucial step that dictated the structure and properties of the final gels. We hypothesized that the primary network formed in the thermal gelation step served as a template for the deposition of chitosan chains during solvent displacement, leading to a homogenous and compact structure. The primary network also provides crystalline seeds to facilitate the crystallization of the chitosan chains, leading to higher degree of crystallinity. This study provided a guideline for the preparation of chitosan hydrogels with high mechanical properties which is very meaningful to relevant research and applications.

Intramammary infusion of matrine-chitosan hydrogels for treating subclinical bovine mastitis -effects on milk microbiome and metabolites.

Background: Bovine metabolism undergoes significant changes during subclinical mastitis, but the relevant molecular mechanisms have not been elucidated. In this study we investigated the changes in milk microbiota and metabolites after intramammary infusion of matrine-chitosan hydrogels (MCHs) in cows with subclinical mastitis. Methods: Infusions were continued for 7 days, and milk samples were collected on days 1 and 7 for microbiome analysis by 16S rRNA gene sequencing and metabolite profiling by liquid chromatography-mass spectrometry. Results: MCHs significantly decreased the somatic cell count on day 7 compared to day 1, and the Simpson index indicated that microbial diversity was significantly lower on day 7. The relative abundance of Aerococcus, Corynebacterium_1, Staphylococcus and Firmicutes was significantly decreased on day 7, while Proteobacteria increased. In the milk samples, we identified 74 differentially expressed metabolites. The MCHs infusion group had the most significantly upregulated metabolites including sphingolipids, glycerophospholipids, flavonoids and fatty acyls. The mammary gland metabolic pathways identified after MCHs treatment were consistent with the known antimicrobial and anti-inflammatory properties of matrine that are associated with glycerophospholipid metabolism and the sphingolipid metabolic signaling pathways. Conclusion: These insights into the immunoregulatory mechanisms and the corresponding biological responses to matrine demonstrate its potential activity in mitigating the harmful effects of bovine mastitis.

Xerogels Morphology Details by Multifractal Analysis and Scanning Electron Microscopy Images Evaluations of 5-Fluorouracil Release from Chitosan-Based Matrix.

Four medicament delivery formulations based on 5-fluorouracil in a chitosan substantial matrix were realized in situ via 3,7-dimethyl-2,6-octadienal element hydrogelation. Representative samples of the final realized compounds were investigated from an analytic, constitutional, and morphological viewpoint via Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). The SEM images of the formulations were investigated in concordance with fractal analysis, and the fractal dimensions and lacunarity were computed. The developed mathematical multifractal model is necessarily confirmed by the experimental measurements corresponding to the 5-fluorouracil release outside the chitosan-formed matrix.