Synthesis of chitosan-graft-methacrylate with enhanced antimicrobial activity for improved mucoadhesive properties and controlled drug delivery systems

Abstract

Chitosan (CS) is a derivative of chitin that displays antimicrobial effects and has other attributes that make it of interest for use in a variety of applications, including drug delivery systems. This study aimed to synthesize chitosan-graft-methacrylate (CS-g-MA) to improve the antimicrobial activities of CS for use in controlled drug delivery systems. CS-g-MA was synthesized via a nucleophilic acyl substitution reaction by gradually adding methacrylic anhydride (MA) to a CS solution until the ratio of CS to MA achieved the maximum degree of substitution. Proton nuclear magnetic resonance spectroscopy and attenuated total reflection-Fourier transformed infrared spectroscopy were used to characterize the resulting polymer. Its mucoadhesive capabilities and cytotoxicity toward human fibroblasts were evaluated, as well as its antimicrobial activities against Staphylococcus aureus, Escherichia coli, and Candida albicans using the minimum inhibitory concentration and minimum bactericidal concentration tests. The optimized CS-g-MA polymer had an optimal weight CS:MA ratio of 3:4 and was combined with sodium fluorescein in tablet form to evaluate drug release. CS-g-MA improved the mucoadhesive capabilities of CS by increasing the number of intermolecular interactions with the grafted moiety. CS-g-MA was non-toxic to normal human fibroblasts and exhibited superior efficacy against S. aureus, E. coli, and C. albicans compared to CS. Furthermore, the CS-g-MA tablet regulated drug release for an extended period of more than 72 h. Thus, CS-g-MA shows significant potential for further development in advanced drug delivery systems.