The present study aims to develop a cationic dextran polymer with improved mucoadhesive properties and high biocompatibility.

Quaternary ammonium-modified dextran was synthesized of dextran via esterification with N-chlorobetainyl chloride. Structural characterizations like zeta potential measurements, ester quantification, NMR, FTIR, and enzymatic degradation studies were performed to confirm the covalent attachment of quaternary ammonium structure to dextran backbone. Biocompatibility of modified dextran was evaluated by in vitro cytotoxic analysis on HeLa and Caco-2 cells, and hemolysis assay. Furthermore, interaction of modified dextran with porcine mucus was evaluated by using plate rheometer. Mucoadhesive properties were investigated on porcine mucosa mimicking in vivo conditions.

A shift in zeta potential from −25.4 ± 0.5 to + 15.6 ± 0.7 mV was obtained for quaternary ammonium-modified dextran with 640.4 ± 9.051 µmol/g ester content. NMR and FTIR analysis confirmed the covalent binding of quaternary ammonium moieties to the polymer backbone. Enzymatic degradation studies demonstrated the lipase-mediated cleavage of quaternary ammonium moieties from modified dextran. Cytotoxicity and hemolysis results proved that quaternary ammonium-modified dextran was not toxic up to the concentration of 0.5 %. Rheometric measurements of quaternary ammonium-modified dextran with mucus showed 2.1- and 3.6-fold higher dynamic viscosity than native polymer at 3 h and 6 h time intervals, respectively. Moreover, compared to native dextran, quaternary ammonium-modified dextran showed 3.4-fold higher mucoadhesive properties on the intestinal mucosa.

Because of its cationic character, quaternary ammonium-modified dextran exhibits promising potential as a biodegradable polymer with improved mucoadhesive properties and remarkable biocompatibility.