Thiol functionalized pH-responsive mucoadhesive hydrogel: Potential approach for site-specific delivery of 5 fluorouracil in colon cancer

The present study aims to develop a novel thiolated carboxymethyl cellulose (CMC-SH) by the addition of aldehyde groups via oxidation followed by reductive amination and then develop CMC-SH based pH-responsive hydrogel by free radical polymerization approach while assessing its mucoadhesive and permeation-enhancing capabilities. By in-vitro characterization, the intended compound's chemical composition, thermal stability, and amorphous nature were analyzed for CMC-SH polymer. Ellman's assay was utilized to estimate the thiol content and permeation analysis was performed to evaluate its enhanced permeability characteristics. The properties of developed CMC-SH based hydrogel were demonstrated by in-vitro analysis, structural, mechanical stability analysis, morphological evaluation and mucoadhesive properties. Rheological data showed that the viscous modulus and elastic modules of CMC-SH rose by 3.5 and 2.1 times, respectively. Compared to FU, the permeation showed a notable improvement of 4.89-fold with CMC-SH. According to an ex-vivo mucoadhesion analysis, CMC-SH based hydrogel was able to adhere to the intestinal mucosal layer for 210 min. The biocompatibility of CMC-SH and CMC-SH based hydrogel was demonstrated using Caco-2 cell lines. Thiolation of carboxymethyl cellulose significantly enhanced its mucoadhesive and permeation qualities, which makes the hydrogel desirable mucoadhesive and selective cytotoxic biomaterial for colorectal cancer therapy. [Display omitted]