Xi Guang Chen

Antimicrobial properties of chitosan and mode of action: A state of the art review

Owing to its high biodegradability, and nontoxicity and antimicrobial properties, chitosan is widely-used as an antimicrobial agent either alone or blended with other natural polymers. To broaden chitosans antimicrobial applicability, comprehensive knowledge of its activity is necessary. The paper reviews the current trend of investigation on antimicrobial activities of chitosan and its mode of action. Chitosan-mediated inhibition is affected by several factors can be classified into four types as intrinsic, environmental, microorganism and physical state, according to their respective roles. In this review, different physical states are comparatively discussed. Mode of antimicrobial action is discussed in parts of the active compound (chitosan) and the target (microorganisms) collectively and independently in same complex. Finally, the general antimicrobial applications of chitosan and perspectives about future studies in this field are considered.

Chemical characteristics of O-carboxymethyl chitosans related to the preparation conditions

Abstract Carboxymethyl chitosan (CM-chitosan) was prepared by chemical reaction with monochloroacetic acid under various conditions, and the chemical structure was analyzed by IR and NMR. The water solubility of the CM-chitosans had close relationships to the modifying conditions and the degree of carboxymethylation. The CM-chitosans, prepared at temperatures of 0–10 °C were soluble in water. But the CM-chitosan prepared between 20 and 60 °C were insoluble in the water at near-neutral pH. The water insolubility of CM-chitosans at various pHs varied with the degree of carboxymethylation. The increase in reaction temperature increased the fraction of carboxymethylation and increased the insolubility at lower pHs; the increase of the ratio of water/isopropanol in the reaction solvent decreased the fraction of carboxymethylation and increased the insolubility at higher pHs.

Antibacterial mechanism of chitosan microspheres in a solid dispersing system against E. coli

In this study, we investigated the antibacterial mechanism through the interfacial contacting inhibition behaviors of chitosan antimicrobials against Escherichia coli in solid dispersing state. Chitosan microspheres (CMs) were prepared by emulsification cross-linking reaction, and oleoyl-CMs (OCMs) were obtained by introduction of oleoyl groups to the chitosan. The CMs were with smooth surface and spherical shape of diameter of about 124 microm. The antibacterial activity was directly proportional to the concentration and the hydrophobic property of CMs. The fluorescence experiments indicated CMs had influenced the structure of membrane, especially the OCMs were speculated to interact with proteins on the cell membrane. SEM photographs showed E. coli adhered to the surface of the CMs and provided evidences for the disruption of the cells, while the bacterium conglomerated on the surface of the OCMs. The CMs changed the permeability of membrane and caused cellular leakage that correlated with the hydrophobic interaction between CMs and cytoplasmic membrane phospholipids of Gram-negative bacteria. Solid dispersing system makes the antibacterial activities of CMs counted as a sequent event-driven to study the antibacterial mechanism of chitosan originally.

The effect of carboxymethyl-chitosan on proliferation and collagen secretion of normal and keloid skin fibroblasts.

In this study, different molecular weight CM-chitosans were prepared and the effects on the growth and collagen secretion of normal skin fibroblasts and keloid fibroblasts were investigated in vitro. CM-chitosan promoted the proliferation of the normal skin fibroblast significantly but inhibited the proliferation of keloid fibroblast. The higher CM-chitosan concentration had a higher initial effect and the lower CM-chitosan concentration had a longer affecting time to the normal skin fibroblast. The lower molecular weight CM-chitosan had significant twofold activities. The CM-chitosan could reduce the ratio of type I/III collagen in keloid fibroblast by inhibiting the secretion of collagen type I; and had no effect on the secretion of types I and III collagen in the normal skin fibroblast.

Glycerophosphate-based chitosan thermosensitive hydrogels and their biomedical applications

Chitosan is non-toxic, biocompatible and biodegradable polysaccharide composed of glucosamine and derived by deacetylation of chitin. Chitosan thermosensitive hydrogel has been developed to form a gel in situ, precluding the need for surgical implantation. In this review, the recent advances in chitosan thermosensitive hydrogels based on different glycerophosphate are summarized. The hydrogel is prepared with chitosan and β-glycerophosphate or αβ-glycerophosphate which is liquid at room temperature and transits into gel as temperature increases. The gelation mechanism may involve multiple interactions between chitosan, glycerophosphate, and water. The solution behavior, rheological and physicochemical properties, and gelation process of the hydrogel are affected not only by the molecule weight, deacetylation degree, and concentration of chitosan, but also by the kind and concentration of glycerophosphate. The properties and the three-dimensional networks of the hydrogel offer them wide applications in biomedical field including local drug delivery and tissue engineering.

Chitosan/o-carboxymethyl chitosan nanoparticles for efficient and safe oral anticancer drug delivery: In vitro and in vivo evaluation

The present study investigated the ability of a polyelectrolyte complex (CS/CMCS-NPs), composed of chitosan (CS) and o-carboxymeymethy chitosan (CMCS) as a pH responsive carrier for oral delivery of doxorubicin hydrochloride (DOX). The obtained CS/CMCS-NPs were characterized for various parameters including morphology, particle size, zeta potential, entrapment efficiency and stability under the simulated GI tract conditions. The pH responsive stability of the DOX-loaded CS/CMCS nanoparticles (DOX:CS/CMCS-NPs) determined the drug release rate, which was lower in acidic pH than the neutral. Ex vivo intestinal adhesion and permeation indicated DOX:CS/CMCS-NGs were able to enhance absorption of DOX throughout the entire small intestine, especially in jejunum and ileum. Oral administration of DOX:CS/CMCS-NPs was effective to deliver DOX into blood, giving an absolute bioavailability of 42%. The tissue distribution and toxicity of DOX:CS/CMCS-NPs in rats showed low level of DOX in heart and kidney, and obviously decreased cardiac and renal toxicities. These results indicated CS/CMCS-NPs were highly efficient and safe as an oral delivery system for DOX.

Oleoyl-chitosan nanoparticles inhibits Escherichia coli and Staphylococcus aureus by damaging the cell membrane and putative binding to extracellular or intracellular targets

A novel chitosan antibacterial dispersion system was prepared by oleoyl-chitosan (OCS) nanoparticles (OCNP). We further investigated the antimicrobial mode of OCNP against Escherichia coli and Staphylococcus aureus using a combination of approaches, including measurement of the effect of lecithin and phosphate groups, the conformation of membrane protein, internalization of fluorescein isothiocyanate (FITC)-labeled OCS nanoparticles (FITC-OCS nanoparticles) observed under fluorescence microscopy and DNA/RNA binding assay. Results of fluorescence experiments indicated that OCNP influenced the structure of bacterial membranes. The lecithin effect showed that OCNP bound to cytoplasmic membrane phospholipids of S. aureus, and phosphate groups played an important role. Fluorescence microscopy observations demonstrated that the way OCNP entered into bacteria varied against strains. The gel-retardation experiment showed that OCNP bound strongly to DNA/RNA and retarded their migration in the gels in a concentration-dependent manner. These results indicate that OCNP exerts its antibacterial activity by damaging the structures of cell membrane and putative binding to extracellular targets such as phosphate groups or intracellular targets such as DNA and RNA.

A Peptide‐Network Weaved Nanoplatform with Tumor Microenvironment Responsiveness and Deep Tissue Penetration Capability for Cancer Therapy

Novel core-shell tumor-penetrating vesicles consisting of a nanovesicle core with tumor-penetrating ligands and enzymatically degradable polymeric peptides anchored covalently to the core to form a thin polymeric shell are evaluated as drug-delivery systems. This delivery platform demonstrates an enhanced therapeutic efficacy attributed to the synergistic contributions from matrix metalloproteinase (MMP)-responsive drug release as well as improved tumor accumulation and penetration in the tumor microenvironment.

Microencapsulation of a probiotic bacteria with alginate–gelatin and its properties

Lactobacillus casei ATCC 393-loaded microcapsules based on alginate and gelatin had been prepared by extrusion method and the product could increase the cell numbers of L. casei ATCC 393 to be 107 CFU g−1 in the dry state of microcapsules. The microparticles homogeneously distributed with size of 1.1 ± 0.2 mm. Four kinds of microcapsules (S1, S2, S3 and S4) exhibited swelling in simulated gastric fluid (SGF) while the beads eroded and disintegrated rapidly in simulated intestinal fluid (SIF). Cells of L. casei ATCC 393 could be continuously released from the microcapsules during simulated gastrointestinal tract (GIT) and the release amounts and speeds in SIF were much higher and faster than that in SGF. Encapsulation in alginate–gelatin microcapsules successfully improved the survival of L. casei ATCC 393 and this approach might be useful in delivery of probiotic cultures as a functional food.

Curcumin-Eudragit® E PO solid dispersion: A simple and potent method to solve the problems of curcumin

Using a simple solution mixing method, curcumin was dispersed in the matrix of Eudragit® E PO polymer. Water solubility of curcumin in curcumin-Eudragit® E PO solid dispersion (Cur@EPO) was greatly increased. Based on the results of several tests, curcumin was demonstrated to exist in the polymer matrix in amorphous state. The interaction between curcumin and the polymer was investigated through Fourier transform infrared spectroscopy and (1)H NMR which implied that OH group of curcumin and carbonyl group of the polymer involved in the H bonding formation. Cur@EPO also provided protection function for curcumin as verified by the pH challenge and UV irradiation test. The pH value influenced curcumin release profile in which sustained release pattern was revealed. Additionally, in vitro transdermal test was conducted to assess the potential of Cur@EPO as a vehicle to deliver curcumin through this alternative administration route.