Abstract

The rational design of thiolated polysaccharides offers new opportunities to enhance the performance of gastroretentive drug delivery systems by improving mucoadhesive and rheological properties. In this study, thiolated carboxymethyl tara gum (CMTG-SH) was synthesized and optimized (DSSH ? 0.9; 2.88 mmol g-1 of thiols) as a novel, sustainable biopolymer. Structural characterization (FTIR, 1HNMR, DSC/TGA, SEM, rheology) confirmed successful thiolation and revealed microstructural and thermal modifications. CMTG-SH showed pH-responsive solubility, increasing from 7 to 12 mg mL-1 (pH 2–3) to 17–40 mg mL-1 (pH 5–6). Oscillatory rheology demonstrated predominant elastic behavior, and mixtures with mucin (1:2 w/w) exhibited a 40-fold increase in storage modulus (?G?/G? = 39.4 ± 2.6 Pa at pH 6.8) and a maximum bioadhesive force (Fbio = 12.9), evidencing strong synergistic interactions. Even under acidic conditions (pH 4.0), positive reinforcement persisted (?G? = 24.9 ± 2.1 Pa). These results establish CMTG-SH as a robust and sustainable thiomer with significant translational potential for gastroretentive and mucosal drug delivery applications. © 2025