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1.
Mar Drugs ; 22(4)2024 Mar 28.
Article En | MEDLINE | ID: mdl-38667767

Chitosan (CH) shows great potential as an immunostimulatory feed additive in aquaculture. This study evaluates the effects of varying dietary CH levels on the growth, immunity, intestinal morphology, and antioxidant status of Nile tilapia (Oreochromis niloticus) reared in a biofloc system. Tilapia fingerlings (mean weight 13.54 ± 0.05 g) were fed diets supplemented with 0 (CH0), 5 (CH5), 10 (CH10), 20 (CH20), and 40 (CH40) mL·kg-1 of CH for 8 weeks. Parameters were assessed after 4 and 8 weeks. Their final weight was not affected by CH supplementation, but CH at 10 mL·kg-1 significantly improved weight gain (WG) and specific growth rate (SGR) compared to the control (p < 0.05) at 8 weeks. Skin mucus lysozyme and peroxidase activities were lower in the chitosan-treated groups at weeks 4 and 8. Intestinal villi length and width were enhanced by 10 and 20 mL·kg-1 CH compared to the control. However, 40 mL·kg-1 CH caused detrimental impacts on the villi and muscular layer. CH supplementation, especially 5-10 mL·kg-1, increased liver and intestinal expressions of interleukin 1 (IL-1), interleukin 8 (IL-8), LPS-binding protein (LBP), glutathione reductase (GSR), glutathione peroxidase (GPX), and glutathione S-transferase (GST-α) compared to the control group. Overall, dietary CH at 10 mL·kg-1 can effectively promote growth, intestinal morphology, innate immunity, and antioxidant capacity in Nile tilapia fingerlings reared in biofloc systems.


Animal Feed , Aquaculture , Chitosan , Cichlids , Intestines , Animals , Chitosan/pharmacology , Cichlids/growth & development , Cichlids/immunology , Cichlids/metabolism , Intestines/drug effects , Aquaculture/methods , Dietary Supplements , Antioxidants/pharmacology , Antioxidants/metabolism , Gene Expression/drug effects
2.
Mar Drugs ; 22(4)2024 Apr 20.
Article En | MEDLINE | ID: mdl-38667805

Three Laminaria japonica polysaccharides (LJPs) extracted via water extraction (LJP-W), acid extraction (LJP-A), and enzymatic extraction (LJP-E) were used as raw materials to be cross-linked with chitosan and polyvinyl alcohol to prepare hydrogels. Compared with conventional hydrogel systems, all three types of LJP-based polysaccharide hydrogels exhibited better swelling properties (14 times their original weight) and the absorption ability of simulated body fluid (first 2 h: 6-10%). They also demonstrated better rigidity and mechanical strength. Young's modulus of LJP-E was 4 times that of the blank. In terms of hemostatic properties, all three polysaccharide hydrogels did not show significant cytotoxic and hemolytic properties. The enzyme- and acid-extracted hydrogels (LJP-Gel-A and LJP-Gel-E) demonstrated better whole-blood coagulant ability compared with the water-extracted hydrogel (LJP-Gel-W), as evidenced by the whole blood coagulation index being half that of LJP-Gel-W. Additionally, the lactate dehydrogenase viabilities of LJP-Gel-A and LJP-Gel-E were significantly higher, at about four and three times those of water extraction, respectively. The above results suggested that LJP-Gel-A and LJP-Gel-E exhibited better blood coagulation capabilities than LJP-Gel-W, due to their enhanced platelet enrichment and adhesion properties. Consequently, these hydrogels are more conducive to promoting coagulation and have good potential for wound hemostasis.


Blood Coagulation , 60578 , Hemostatics , Hydrogels , Laminaria , Polysaccharides , Hydrogels/chemistry , Hydrogels/pharmacology , Laminaria/chemistry , Polysaccharides/chemistry , Polysaccharides/pharmacology , Polysaccharides/isolation & purification , Blood Coagulation/drug effects , Hemostatics/pharmacology , Hemostatics/chemistry , Hemostatics/isolation & purification , Humans , Animals , Chitosan/chemistry , Chitosan/pharmacology , Polyvinyl Alcohol/chemistry , Hemostasis/drug effects , Hemolysis/drug effects
3.
Sci Rep ; 14(1): 7624, 2024 04 01.
Article En | MEDLINE | ID: mdl-38561345

It is known that titanium (Ti) implant surfaces exhibit poor antibacterial properties and osteogenesis. In this study, chitosan particles loaded with aspirin, amoxicillin or aspirin + amoxicillin were synthesized and coated onto implant surfaces. In addition to analysing the surface characteristics of the modified Ti surfaces, the effects of the modified Ti surfaces on the adhesion and viability of rat bone marrow-derived stem cells (rBMSCs) were evaluated. The metabolic activities of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) biofilms on the modified Ti surfaces were also measured in vitro. Moreover, S. aureus was tested for its antibacterial effect by coating it in vivo. Using water as the droplet medium, the contact angles of the modified Ti surfaces increased from 44.12 ± 1.75° to 58.37 ± 4.15°. In comparison to those of the other groups tested, significant increases in rBMSC adhesion and proliferation were observed in the presence of aspirin + amoxicillin-loaded microspheres, whereas a significant reduction in the metabolic level of biofilms was observed in the presence of aspirin + amoxicillin-loaded microspheres both in vitro and in vivo. Aspirin and amoxicillin could be used in combination to coat implant surfaces to mitigate bacterial activities and promote osteogenesis.


Amoxicillin , Chitosan , Indoles , Polymers , Rats , Animals , Amoxicillin/pharmacology , Aspirin/pharmacology , Titanium/pharmacology , Chitosan/pharmacology , Osteogenesis , Staphylococcus aureus , Escherichia coli , Anti-Bacterial Agents/pharmacology , Surface Properties , Coated Materials, Biocompatible/pharmacology
4.
BMC Vet Res ; 20(1): 130, 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38561827

BACKGROUND: Growing antibiotic resistance has made treating otitis externa (OE) increasingly challenging. On the other hand, local antimicrobial treatments, especially those that combine essential oils (EOs) with nanoparticles, tend to be preferred over systemic ones. It was investigated whether Ajwain (Trachyspermum ammi) EO, combined with chitosan nanoparticles modified by cholesterol, could inhibit the growth of bacterial pathogens isolated from OE cases in dogs. In total, 57 dogs with clinical signs of OE were examined and bacteriologically tested. Hydrogels of Chitosan were synthesized by self-assembly and investigated. EO was extracted (Clevenger machine), and its ingredients were checked (GC-MS analysis) and encapsulated in chitosan-cholesterol nanoparticles. Disc-diffusion and broth Micro-dilution (MIC and MBC) examined its antimicrobial and therapeutic properties. RESULTS: Staphylococcus pseudintermedius (49.3%) was the most common bacteria isolated from OE cases, followed by Pseudomonas aeruginosa (14.7%), Escherichia coli (13.3%), Streptococcus canis (9.3%), Corynebacterium auriscanis (6.7%), Klebsiella pneumoniae (2.7%), Proteus mirabilis (2.7%), and Bacillus cereus (1.3%). The investigation into the antimicrobial properties of Ajwain EO encapsulated in chitosan nanoparticles revealed that it exhibited a more pronounced antimicrobial effect against the pathogens responsible for OE. CONCLUSIONS: Using chitosan nanoparticles encapsulated with EO presents an effective treatment approach for dogs with OE that conventional antimicrobial treatments have not cured. This approach not only enhances antibacterial effects but also reduces the required dosage of antimicrobials, potentially preventing the emergence of antimicrobial resistance.


Ammi , Anti-Infective Agents , Chitosan , Dog Diseases , Oils, Volatile , Otitis Externa , Dogs , Animals , Oils, Volatile/pharmacology , Chitosan/pharmacology , Otitis Externa/drug therapy , Otitis Externa/veterinary , Otitis Externa/microbiology , Microbial Sensitivity Tests/veterinary , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents/therapeutic use , Bacteria , Escherichia coli , Cholesterol , Dog Diseases/drug therapy , Dog Diseases/microbiology
5.
J Vet Sci ; 25(2): e30, 2024 Mar.
Article En | MEDLINE | ID: mdl-38568831

BACKGROUND: Biofilms, such as those from Staphylococcus epidermidis, are generally insensitive to traditional antimicrobial agents, making it difficult to inhibit their formation. Although quercetin has excellent antibiofilm effects, its clinical applications are limited by the lack of sustained and targeted release at the site of S. epidermidis infection. OBJECTIVES: Polyethylene glycol-quercetin nanoparticles (PQ-NPs)-loaded gelatin-N,O-carboxymethyl chitosan (N,O-CMCS) composite nanogels were prepared and assessed for the on-demand release potential for reducing S. epidermidis biofilm formation. METHODS: The formation mechanism, physicochemical characterization, and antibiofilm activity of PQ-nanogels against S. epidermidis were studied. RESULTS: Physicochemical characterization confirmed that PQ-nanogels had been prepared by the electrostatic interactions between gelatin and N,O-CMCS with sodium tripolyphosphate. The PQ-nanogels exhibited obvious pH and gelatinase-responsive to achieve on-demand release in the micro-environment (pH 5.5 and gelatinase) of S. epidermidis. In addition, PQ-nanogels had excellent antibiofilm activity, and the potential antibiofilm mechanism may enhance its antibiofilm activity by reducing its relative biofilm formation, surface hydrophobicity, exopolysaccharides production, and eDNA production. CONCLUSIONS: This study will guide the development of the dual responsiveness (pH and gelatinase) of nanogels to achieve on-demand release for reducing S. epidermidis biofilm formation.


Chitosan , Nanoparticles , Animals , Staphylococcus epidermidis/genetics , Nanogels , Gelatin/pharmacology , Quercetin/pharmacology , Biofilms , Chitosan/pharmacology , Chitosan/chemistry , Gelatinases/pharmacology , Anti-Bacterial Agents/pharmacology
6.
Vet Med Sci ; 10(3): e1440, 2024 May.
Article En | MEDLINE | ID: mdl-38613443

BACKGROUND: Honey exhibits a broad spectrum of antibacterial activity against Gram-positive and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) ones. Chitosan (Cs) is a mucoadhesive polymer that also has antibacterial properties. Special attention has been paid to the design of polymeric nanoparticles (NPs) as new nano drug delivery systems to overcome bacterial resistance and its problems. OBJECTIVES: The aim of the present study is to synthesize Cs-meropenem NPs with/without honey as an antibiofilm and antibacterial agent to inhibit Staphylococcus aureus. METHODS: This study synthesized meropenem and honey-loaded Cs nanogels and subsequently characterized them by Field Emission Scanning Electron Microscopy (FESEM), Fourier Transform Infrared Spectroscopy (FTIR), and DLS-zeta potential. Using the broth microdilution and crystal violet assays, the antibacterial and antibiofilm activity of meropenem and honey-loaded Cs nanogel, free meropenem, free honey, and free Cs NPs were investigated in vitro against MRSA strains. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) was also used to test the cytotoxicity of several Cs-NPs compound against the HEK-293 regular cell line. RESULTS: The average size of meropenem and honey-Cs-NPs was reported to be 119.885 nm, and encapsulation efficiency was 88.33 ± 0.97 with stability up to 60 days at 4°C. The NPs showed enhanced antibiofilm efficacy against S. aureus at sub-minimum inhibitory concentrations. Additionally, the cytotoxicity of meropenem and honey-encapsulated Cs against the HEK-293 normal cell line was insignificant. CONCLUSIONS: Our findings suggested that meropenem and honey-Cs-NPs might be potential antibacterial and antibiofilm materials.


Anti-Infective Agents , Chitosan , Honey , Methicillin-Resistant Staphylococcus aureus , Nanoparticles , Staphylococcal Infections , Animals , Humans , Meropenem/pharmacology , Staphylococcus aureus , Anti-Bacterial Agents/pharmacology , Chitosan/pharmacology , HEK293 Cells , Gram-Negative Bacteria , Gram-Positive Bacteria , Staphylococcal Infections/veterinary , Biofilms
7.
Open Vet J ; 14(1): 416-427, 2024 Jan.
Article En | MEDLINE | ID: mdl-38633182

Background: Acute lung injury (ALI) is a severe condition distinguished by inflammation and impaired gas exchange in the lungs. Staphylococcus aureus, a common bacterium, can cause ALI through its virulence factors. Aloe vera is a medicinal plant that has been traditionally used to treat a variety of illnesses due to its anti-inflammatory properties. Chitosan nanoparticles are biocompatible and totally biodegradable materials that have shown potential in drug delivery systems. Aim: To explore the antibacterial activity of Aloe vera-loaded chitosan nanoparticles (AV-CS-NPs) against S. aureus in vitro and in vivo with advanced techniques. Methods: The antibacterial efficacy of AV-CS-NPs was evaluated through a broth microdilution assay. In addition, the impact of AV-CS-NPs on S. aureus-induced ALI in rats was examined by analyzing the expression of genes linked to inflammation, oxidative stress, and apoptosis. Furthermore, rat lung tissue was scanned histologically. The rats were divided into three groups: control, ALI, and treatment with AV-CS-NPs. Results: The AV-CS-NPs that were prepared exhibited clustered semispherical and spherical forms, having an average particle size of approximately 60 nm. These nanoparticles displayed a diverse structure with an uneven distribution of particle sizes. The maximum entrapment efficiency of 95.5% ± 1.25% was achieved. The obtained findings revealed that The minimum inhibitory concentration and minimum bactericidal concentration values were determined to be 5 and 10 ug/ml, respectively, indicating the potent bactericidal effect of the NPs. Also, S. aureus infected rats explored upregulation in the mRNA expression of TLR2 and TLR4 compared to healthy control groups. AV-CS-NP treatment reverses the case where there was repression in mRNA expression of TLR2 and TLR4 compared to S. aureus-treated rats. Conclusion: These NPs can serve as potential candidates for the development of alternative antimicrobial agents.


Acute Lung Injury , Aloe , Chitosan , Nanoparticles , Rodent Diseases , Rats , Animals , Chitosan/chemistry , Chitosan/pharmacology , NF-kappa B/pharmacology , Staphylococcus aureus , Toll-Like Receptor 2 , Toll-Like Receptor 4 , Nanoparticles/chemistry , Signal Transduction , Anti-Bacterial Agents/pharmacology , Acute Lung Injury/veterinary , Inflammation/veterinary , RNA, Messenger/pharmacology
8.
Sci Rep ; 14(1): 9348, 2024 04 23.
Article En | MEDLINE | ID: mdl-38654048

This study investigates the creation and analysis of chitosan-zinc oxide (CS-ZnO) nanocomposites, exploring their effectiveness in inhibiting bacteria. Two synthesis approaches, physical and chemical, were utilized. The CS-ZnO nanocomposites demonstrated strong antibacterial properties, especially against Staphylococcus aureus, a Gram-positive bacterium. Chemically synthesized nanocomposites (CZ10 and CZ100) exhibited larger inhibition zones (16.4 mm and 18.7 mm) compared to physically prepared CS-Z5 and CS-Z20 (12.2 mm and 13.8 mm) against Staphylococcus aureus. Moreover, CZ nanocomposites displayed enhanced thermal stability, with decomposition temperatures of 281°C and 290°C, surpassing CS-Z5 and CS-Z20 (260°C and 258°C). The residual mass percentages at 800°C were significantly higher for CZ10 and CZ100 (58% and 61%) than for CS-Z5 and CS-Z20 (36% and 34%). UV-Visible spectroscopy revealed reduced band gaps in the CS-ZnO nanocomposites, indicating improved light absorption. Transmission electron microscopy (TEM) confirmed uniform dispersion of ZnO nanoparticles within the chitosan matrix. In conclusion, this research underscores the impressive antimicrobial potential of CS-ZnO nanocomposites, especially against Gram-positive bacteria, and highlights their enhanced thermal stability. These findings hold promise for diverse applications in industries such as medicine, pharmaceuticals, and materials science, contributing to the development of sustainable materials with robust antimicrobial properties.


Anti-Bacterial Agents , Chitosan , Microwaves , Nanocomposites , Staphylococcus aureus , Zinc Oxide , Chitosan/chemistry , Chitosan/pharmacology , Zinc Oxide/chemistry , Zinc Oxide/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Nanocomposites/chemistry , Staphylococcus aureus/drug effects , Microbial Sensitivity Tests
9.
J Wound Care ; 33(Sup4a): cxi-cxvii, 2024 Apr 02.
Article En | MEDLINE | ID: mdl-38588055

OBJECTIVE: Scar tissue formation, as a normal part of wound healing, initiates in the proliferation phase, continues after the remodelling phase, and may cause an unpleasant appearance or disruption in normal functioning. This study investigated the effects of a topical gel on acute wound healing and reducing scars in a rat model. METHOD: ChitoScar (ChitoTech Company, Iran), a commercial scar-reducing gel based on chitosan, was analysed for antibacterial and antiviral activity through a quantitative suspension test. Its cytotoxic effect was investigated, and then irritation and delayed-type hypersensitivity tests were carried out on rabbits through direct application of the gel. Furthermore, the effect of the chitosan-based gel on wound healing and scar tissue formation was studied in rats with an acute wound in two groups: the treatment group (topical application of the chitosan-based gel); and the control group (without treatment). Histopathological examination was carried out based on the inflammatory cells, collagen fibre, keratinocytes and fibroblasts. RESULTS: Analysis revealed that the chitosan-based gel had no cytotoxicity and caused no erythema, oedema, local or other systemic adverse response. Wound healing occurred earlier in the treatment group, which was a result of a significant increase in re-epithelialisation, angiogenesis, fibroblast population and collagen fibre thickness (p<0.05). In the treatment group, wounds healed completely after 21 days and scars totally disappeared after 28 days, while in the control group, wound healing remained incomplete with distinct scar tissue. CONCLUSION: The results demonstrated the positive effect of the chitosan-based gel on the duration and quality of the wound healing process, as well as minimising the scar tissue formation in this in vivo study.


Chitosan , Cicatrix , Rats , Rabbits , Animals , Chitosan/pharmacology , Chitosan/therapeutic use , Wound Healing , Skin , Collagen/pharmacology
10.
Carbohydr Polym ; 332: 121914, 2024 May 15.
Article En | MEDLINE | ID: mdl-38431416

Chitosan oligosaccharide (COS), which represent the positively charged basic amino oligosaccharide in nature, is the deacetylated and degraded products of chitin. COS has become the focus of intensive scientific investigation, with a growing body of practical and clinical studies highlighting its remarkable health-enhancing benefits. These effects encompass a wide range of properties, including antibacterial, antioxidant, anti-inflammatory, and anti-tumor activities. With the rapid advancements in chemical modification technology for oligosaccharides, many COS derivatives have been synthesized and investigated. These newly developed derivatives possess more stable chemical structures, improved biological activities, and find applications across a broader spectrum of fields. Given the recent interest in the chemical modification of COS, this comprehensive review seeks to consolidate knowledge regarding the preparation methods for COS derivatives, alongside discussions on their structural characterization. Additionally, various biological activities of COS derivatives have been discussed in detail. Lastly, the potential applications of COS derivatives in biomedicine have been reviewed and presented.


Chitosan , Chitosan/pharmacology , Chitosan/chemistry , Chitin/chemistry , Oligosaccharides/pharmacology , Oligosaccharides/chemistry , Anti-Bacterial Agents , Antioxidants/pharmacology
11.
Arch Microbiol ; 206(3): 133, 2024 Mar 02.
Article En | MEDLINE | ID: mdl-38430254

In recent years, the study of essential oils as antifungal alternatives and their encapsulation to increase their properties for greater effects has been tested. In this work, nanoparticles of chitosan-Schinus molle L. essential oil (CS-PEO-Np) with a size of 260 ± 31.1 nm were obtained by ionic gelation and evaluated in some growth phases of Aspergillus flavus, a toxigenic fungus. At a concentration of 250 µg/mL of CS-PEO-Np, the A. flavus mycelial growth was inhibited at 97.1% with respect to control, at 96 h of incubation; the germination and viability of spores were inhibited at 74.8 and 40%, respectively, after exposure to 500 µg/mL of these nanomaterials, at 12 h of incubation. The fluorescence images of stained spores with DAPI showed the affectations caused by nanoparticles in the cell membrane, vacuoles and vacuolar content, cell wall, and nucleic acids. For both nanoparticles, CS-Np and CS-PEO-Np, no mutagenic effect was observed in Salmonella Typhimurium; also, the phytotoxic assay showed low-to-moderate toxicity toward seeds, which was dependent on the nanoparticle's concentration. The acute toxicity of CS-PEO-Np to A. salina nauplii was considered low in comparison to CS-Np (control), which indicates that the incorporation of Schinus molle essential oil into nanoparticles of chitosan is a strategy to reduce the toxicity commonly associated with nanostructured materials. The nanoparticulated systems of CS-PEO-Np represent an effective and non-toxic alternative for the control of toxigenic fungi such as A. flavus by delaying the initial growth stage.


Chitosan , Nanoparticles , Oils, Volatile , Oils, Volatile/pharmacology , Aspergillus flavus , Chitosan/pharmacology , Schinus , Antifungal Agents/toxicity , Antifungal Agents/metabolism
12.
J Biomed Mater Res B Appl Biomater ; 112(3): e35397, 2024 Mar.
Article En | MEDLINE | ID: mdl-38456309

In this study, we have formulated a novel apatite bone cements derived from natural sources (i.e. eggshell and fishbone) with improved qualities that is, porosity, resorbability, biological activity, and so forth. The naturally-derived apatite bone cement (i.e. FBDEAp) was prepared by mixing hydroxyapatite (synthesized from fishbone) and tricalcium phosphate (synthesized from eggshell) as a solid phase with a liquid phase (a dilute acidic blend of cement binding accelerator and biopolymers like gelatin and chitosan) with polysorbate (as liquid porogen) to get a desired bone cement paste. The prepared cement paste sets within the clinically acceptable setting time (≤20 min), easily injectable (>85%) through hands and exhibits physiological pH stability (7.3-7.4). The pure apatite phased bone cement was confirmed by x-ray diffraction and Fourier transform infrared spectroscopy analyses. The FBDEAp bone cement possesses acceptable compressive strength (i.e. 5-7 MPa) within trabecular bone range and is resorbable up to 28% in simulated body fluid solution within 12 weeks of incubation at physiological conditions. The FBDEAp is macroporous in nature (average pore size ~50-400 µm) with interconnected pores verified by SEM and micro-CT analyses. The FBDEAp showed significantly increased MG63 cell viability (>125% after 72 h), cell adhesion, proliferation, and key osteogenic genes expression levels (up to 5-13 folds) compared to the synthetically derived, synthetic and eggshell derived as well as synthetic and fishbone derived bone cements. Thus, we strongly believe that our prepared FBDEAp bone cement can be used as potential trabecular bone substitute in orthopedics.


Bone Substitutes , Chitosan , Apatites/pharmacology , Apatites/chemistry , Bone Substitutes/chemistry , Bone Cements/pharmacology , Bone Cements/chemistry , Calcium Phosphates/chemistry , Durapatite , Chitosan/pharmacology , Chitosan/chemistry , X-Ray Diffraction , Compressive Strength
13.
Int J Nanomedicine ; 19: 2265-2284, 2024.
Article En | MEDLINE | ID: mdl-38476273

Introduction: Glaucoma is a prevalent cause of irreversible vision impairment, characterized by progressive retinal ganglion cells (RGCs) loss, with no currently available effective treatment. Rapamycin (RAPA), an autophagy inducer, has been reported to treat glaucoma in rodent models by promoting RGC survival, but its limited water solubility, systemic toxicity, and pre-treatment requirements hinder its potential clinical applications. Methods: Chitosan (CS)-RAPA carbon dot (CRCD) was synthesized via hydrothermal carbonization of CS and RAPA and characterized by transmission electron microscopy, Fourier transform infrared spectra, and proton nuclear magnetic resonance. In vitro assays on human umbilical cord vein endothelial and rat retinal cell line examined its biocompatibility and anti-oxidative capabilities, while lipopolysaccharide-stimulated murine microglia (BV2) assays measured its effects on microglial polarization. In vivo, using a mouse retinal ischemia/reperfusion (I/R) model by acute intraocular pressure elevation, the effects of CRCD on visual function, RGC apoptosis, oxidative stress, and M2 microglial polarization were examined. Results: CRCD exhibited good water solubility and anti-oxidative capabilities, in the form of free radical scavenging. In vitro, CRCD was bio-compatible and lowered oxidative stress, which was also found in vivo in the retinal I/R model. Additionally, both in vitro with lipopolysaccharide-stimulated BV2 cells and in vivo with the I/R model, CRCD was able to promote M2 microglial polarization by activating autophagy, which, in turn, down-regulated pro-inflammatory cytokines, such as IL-1ß and TNF-α, as well as up-regulated anti-inflammatory cytokines, such as IL-4 and TGF-ß. All these anti-oxidative and anti-inflammatory effects ultimately aided in preserving RGCs, and subsequently, improved visual function. Discussion: CRCD could serve as a potential novel treatment strategy for glaucoma, via incorporating RAPA into CDs, in turn not only mitigating its toxic side effects but also enhancing its therapeutic efficacy.


Chitosan , Glaucoma , Reperfusion Injury , Rats , Animals , Mice , Humans , Microglia/pathology , Chitosan/pharmacology , Sirolimus/pharmacology , Carbon/pharmacology , Lipopolysaccharides/pharmacology , Glaucoma/drug therapy , Anti-Inflammatory Agents/pharmacology , Disease Models, Animal , Autophagy , Cytokines/metabolism , Water , Reperfusion Injury/drug therapy
14.
Sci Rep ; 14(1): 7505, 2024 03 29.
Article En | MEDLINE | ID: mdl-38553565

Addressing the increasing drug resistance in pathogenic microbes, a significant threat to public health, calls for the development of innovative antibacterial agents with versatile capabilities. To enhance the antimicrobial activity of non-toxic biomaterials in this regard, this study focuses on novel, cost-effective chitosan (CS)-based hydrogels, crosslinked using gelatin (GEL), formaldehyde, and metallic salts (Ag+, Cu2+, and Zn2+). These hydrogels are formed by mixing CS and GEL with formaldehyde, creating iminium ion crosslinks with metallic salts without hazardous crosslinkers. Characterization techniques like FTIR, XRD, FESEM, EDX, and rheological tests were employed. FTIR analysis showed metal ions binding to amino and hydroxyl groups on CS, enhancing hydrogelation. FESEM revealed that freeze-dried hydrogels possess a crosslinked, porous structure influenced by various metal ions. Antibacterial testing against gram-negative and gram-positive bacteria demonstrated significant bacterial growth inhibition. CS-based hydrogels containing metal ions showed reduced MIC and MBC values against Staphylococcus aureus (0.5, 8, 16 µg/mL) and Escherichia coli (1, 16, 8 µg/mL) for CS-g-GEL-Ag+, CS-g-GEL-Cu2+, and CS-g-GEL-Zn2+. MTT assay results confirmed high biocompatibility (84.27%, 85.24%, 84.96% viability at 10 µg/mL) for CS-based hydrogels towards HFF-1 cells over 48 h. Therefore, due to their non-toxic nature, these CS hydrogels are promising for antibacterial applications.


Chitosan , Chitosan/pharmacology , Chitosan/chemistry , Gelatin/pharmacology , Gelatin/chemistry , Porosity , Salts , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Biocompatible Materials/pharmacology , Biocompatible Materials/chemistry , Metals , Formaldehyde , Hydrogels/pharmacology , Hydrogels/chemistry , Ions
15.
Int J Biol Macromol ; 265(Pt 2): 130825, 2024 Apr.
Article En | MEDLINE | ID: mdl-38492705

The inflammation of chronic wounds plays a key hindering role in the wound healing process. Slowing down the inflammatory response is significant for the repair of chronic wounds. Studies have revealed that succinate can inactivate gastrin D (GSDMD) and prevent cell pyroptosis. Chitosan has anti-inflammatory properties and is commonly used as wound healing material. Therefore, we used succinic anhydride to modify chitosan and found that N-succinylated chitosan (NSC) was more effective in inhibiting inflammation. The results showed that the stimulation of TNF-α and high glucose induces overexpression of capase-1 and TNF-α in human umbilical vein endothelial cells (HUVEC), and down-expression of CD31. However, the expression of capase-1 and TNF-α decreased, while the expression of CD31, VEGF and IL-10 was up-regulated significantly in dysfunctional HUVEC cells after treated by NSC. Moreover, NSC can speed wound healing, histological examination results showed that wounds treated with NSC exhibited faster epithelial tissue regeneration and thicker collagen deposition. Overall, this study results suggested that NSC has the function of restoring the physiological functions of dysfunctional HUVEC cells induced by high glucose and TNF-α, and can accelerate wound healing, indicating that NSC has good potential to be applied in inflammatory chronic wounds such as diabetic foot.


Chitosan , Humans , Chitosan/pharmacology , Tumor Necrosis Factor-alpha/metabolism , Human Umbilical Vein Endothelial Cells/metabolism , Wound Healing , Inflammation/pathology , Glucose/pharmacology
16.
Int J Biol Macromol ; 265(Pt 2): 130950, 2024 Apr.
Article En | MEDLINE | ID: mdl-38513911

Due to its outstanding qualities, particularly when it takes the shape of hydrogels, chitosan is a well-known biological macromolecule with many applications. When chitosan hydrogels are modified with other polymers, the desirable function as skin regeneration hydrogels is compromised; nevertheless, the mechanical properties can be improved, which is crucial for commercialization. In this study, for the first time, bimetallic zinc silver metal-organic frameworks (ZAg MOF) loaded with ascorbic acid were added to chitosan/polyethylene oxide (PEO) based interpenetrating polymer network (IPN) hydrogels that were crosslinked with biotin to improve their antimicrobial activity, mechanical characteristics, and sustainable treatment of wounds. Significant changes in the microstructure, hydrophilicity level, and mechanical properties were noticed. Ascorbic acid release patterns were upregulated in an acidic environment pH (5.5) that mimics the initial wound pH. Impressive cell viability (98 %), antimicrobial properties, and almost full skin healing in a short time were achieved for the non-replaceable chitosan/PEO developed hydrogels. Enhancing the wound healing of the treated animals using the prepared CS/PEO hydrogel dressing was found to be a result of the inhibition of dermal inflammation via decreasing IL-1ß, suppressing ECM degradation (MMP9), stimulating proliferation through upregulation of TGF-ß and increasing ECM synthesis as it elevates collagen 1 and α-SMA contents. The findings support the implementation of developed hydrogels as antimicrobial hydrogels dressing for fast skin regeneration.


Chitosan , Animals , Chitosan/pharmacology , Chitosan/chemistry , Polyethylene Glycols/pharmacology , Anti-Bacterial Agents/chemistry , Hydrogels/pharmacology , Hydrogels/chemistry , Polymers , Ascorbic Acid
17.
Int J Biol Macromol ; 265(Pt 2): 130654, 2024 Apr.
Article En | MEDLINE | ID: mdl-38553395

AIM AND BACKGROUND: Trinitroglycerin (TNG) is a remarkable NO-releasing agent. Here, we synthesized TNG based on chitosan Nanogels (Ngs) for ameliorating complications associated with high-dose TNG administration. METHOD: TNG-Ngs fabricated through ionic-gelation technique. Fourier-transformed infrared (FT-IR), zeta-potential, dynamic light scattering (DLS), and electron microscopy techniques evaluated the physicochemical properties of TNG-Ngs. MTT was used to assess the biocompatibility of TNG-Ngs, as the antioxidative properties were determined via lactate dehydrogenase (LDH), reactive oxygen species (ROS), and lipid peroxide (LPO) assays. The antibacterial activity was evaluated against Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), Methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococci (VRE). RESULTS: Physicochemical characterization reveals that TNG-Ngs with size diameter (96.2 ± 29 nm), polydispersity index (PDI, 0.732), and negative zeta potential (-1.1 mv) were fabricated. The encapsulation efficacy (EE) and loading capacity (LC) were obtained at 71.1 % and 2.3 %, respectively, with no considerable effect on particle size and morphology. The cytotoxicity assay demonstrated that HepG2 cells exposed to TNG-Ngs showed relative cell viability (RCV) of >80 % for 70 µg/ml compared to the TNG-free drug at the same concentration (P < 0.05). TNG-Ngs showed significant differences with the TNG-free drug for LDH, LPO, and ROS formation at the same concentration (P < 0.001). The antibacterial activity of the TNG-Ngs against S. aureus, E. coli, VRE, and MRSA was higher than the TNG-free drug and Ngs (P < 0.05). CONCLUSION: TNG-Ngs with enhanced antibacterial and antioxidative activity and no obvious cytotoxicity might be afforded as novel nanoformulation for promoting NO-dependent diseases.


Chitosan , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Humans , Nanogels , Chitosan/pharmacology , Chitosan/chemistry , Staphylococcus aureus , Escherichia coli , Spectroscopy, Fourier Transform Infrared , Reactive Oxygen Species/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry
18.
Int J Biol Macromol ; 264(Pt 2): 130663, 2024 Apr.
Article En | MEDLINE | ID: mdl-38453104

Diabetic nephropathy (DN) is a serious complication in patients with diabetes, whose expansion process is closely related to oxidative stress caused by hyperglycemia. Herein, we report a chitosan-targeted dagliflozin-loaded melanin nanoparticle (CSMDNPs) that can selectively accumulate in injured kidneys, reduce blood glucose, and alleviate the oxidative stress-induced damage. CSMDNPs possess good dispersion and physiological stability, responsive release at acidic pH, and strong scavenging activities for various reactive oxygen and reactive nitrogen radicals. Moreover, in vitro experiments confirm that CSMDNPs have good biocompatibility, enable targeted uptake in NRK-52E renal tubular cells, and also well alleviate high glucose-induced oxidative stress. In the STZ-induced DN model, CSMDNPs exhibit high targeting distribution and retention in the damaged kidneys of DN mice according to photoacoustic imaging. At the end of CSMDNPs treatment, DN mice show a decrease in fasting blood glucose and a return to near-normal urine and blood indices. H&E, PAS, and masson pathological staining also indicates that CSMDNPs significantly inhibit the expansion of renal interstitium, glycogen, and collagen deposition, showing excellent therapeutic effects. In addition, melanin acts as both drug carrier and antioxidant without exogenous carrier introduction, exhibiting better biosafety and translational prospects.


Chitosan , Diabetes Mellitus , Diabetic Nephropathies , Humans , Animals , Mice , Diabetic Nephropathies/pathology , Blood Glucose/metabolism , Melanins/metabolism , Chitosan/pharmacology , Kidney , Oxidative Stress , Diabetes Mellitus/metabolism
19.
Int J Biol Macromol ; 264(Pt 2): 130625, 2024 Apr.
Article En | MEDLINE | ID: mdl-38458295

Electrical stimulation modulates cell behavior and influences bacterial activity, so highly conductive, antimicrobial hydrogels are suitable for promoting wound healing. In this study, highly conductive and antimicrobial Ti3C2Tx (MXene) hydrogels composed of chitosan and poly(vinyl alcohol) and AgCu- H2PYDC MOF were developed. In PVACS/MOF/MXene (PCMM) hydrogels, the MXene layer acts as an electrical conductor. The electrical conductivity is 0.61 ± 0.01 S·cm-1. PCMM hydrogels modulate cell behavior and provide ES antimicrobial capacity under ES at 1 V. The metal ions of MOF form coordination with chitosan molecules and increase the cross-linking density between chitosan molecules, thus improving the mechanical properties of the hydrogel (tensile strength 0.088 ± 0.04 MPa, elongation at break 233 ± 11 %). The PCMM gels had good biocompatibility. The PCMM hydrogels achieved 100 % antibacterial activity against E. coli and S. aureus for 12 h. 1 V electrical stimulation of PCMM hydrogel accelerated the wound healing process in mice by promoting cell migration and neovascularization, achieving 97 ± 0.4 % wound healing on day 14. The hydrogel dressing PCMM-0.1 with MOF addition of 0.1 % had the best wound healing promoting effect and which is a promising dressing for promoting wound healing and is a therapeutic strategy worth developing.


Chitosan , Nitrites , Transition Elements , Mice , Animals , Chitosan/pharmacology , Hydrogels/pharmacology , Escherichia coli , Staphylococcus aureus , Wound Healing , Anti-Bacterial Agents/pharmacology
20.
Int J Biol Macromol ; 264(Pt 2): 130672, 2024 Apr.
Article En | MEDLINE | ID: mdl-38462095

The long-term application of plant essential oils in food preservation coatings is limited by their poor water solubility and high volatility, despite their recognized synergistic antimicrobial effects in postharvest fruit preservation. To overcome these limitations, a Pickering emulsion loaded with thyme essential oil (TEO) was developed by utilizing hydrogen bonding and electrostatic interactions to induce cross-linking of chitosan particles. This novel emulsion was subsequently applied in the postharvest storage of strawberries. The shear-thinning behavior (flow index <1) and elastic gel-like characteristics of the emulsion made it highly suitable for spray application. Regarding TEO release, the headspace concentration of TEO increased from 0.21 g/L for pure TEO to 1.86 g/L after two instances of gas release due to the stabilizing effect of the chitosan particles at the oil-water interface. Notably, no phase separation was observed during the 10-day storage of the emulsion. Consequently, the emulsion was successfully employed for the postharvest storage of strawberries, effectively preventing undesirable phenomena such as weight loss, a decrease in firmness, an increase in pH, and microbial growth. In conclusion, the developed Pickering emulsion coating exhibits significant potential for fruit preservation applications, particularly for extending the shelf life of strawberries.


Chitosan , Fragaria , Oils, Volatile , Plant Oils , Thymol , Thymus Plant , Chitosan/pharmacology , Emulsions , Food Preservation , Oils, Volatile/pharmacology , Water
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