Comparative Release Kinetics and Mechanistic Modeling of Mesalazine from PEGylated Chitosan-Coated Niosomes

Abstract

Mesalazine is widely used in the treatment of inflammatory bowel diseases; however, its therapeutic efficacy may be limited by rapid drug release and insufficient retention at the target site. In the present study, PEGylated chitosan-coated niosomes (PEG-CS-MEZ-NIO) were developed as a controlled-release delivery system for mesalazine. The formulation was prepared using the thin-film hydration method followed by chitosan surface modification. Encapsulation efficiency, permeability, in vitro drug release behavior, and release kinetics were investigated. The prepared formulation exhibited a high encapsulation efficiency of 95.42%, indicating effective drug entrapment within the vesicular structure. Permeability studies demonstrated excellent storage stability with minimal drug leakage under refrigerated conditions. In vitro release studies revealed a biphasic release profile characterized by an initial burst release followed by a sustained release phase, reaching a cumulative release of 29.8% after 270 min. To elucidate the release mechanism, the experimental data were fitted to zero-order, first-order, Higuchi, and Korsmeyer-Peppas kinetic models. Among the investigated models, the Higuchi model provided the highest correlation coefficient (R^²=0.9990), suggesting diffusion-controlled release as the predominant mechanism. Furthermore, the Korsmeyer-Peppas model yielded a release exponent of n=0.8852, indicating anomalous (non-Fickian) transport involving both diffusion and polymer relaxation processes. The findings demonstrate that PEGylated chitosan-coated niosomes can effectively regulate mesalazine release and represent a promising platform for sustained drug delivery applications.