Thiolated pectin-chitosan composites: Potential mucoadhesive drug delivery system with selective cytotoxicity towards colorectal cancer

Mucoadhesive drug delivery systems (DDS) may promote safer chemotherapy for colorectal cancer (CRC) by maximizing local drug distribution and residence time. Carbohydrate polymers, e.g. pectin (P) and chitosan (CS), are potential biomaterials for CRC-targeted DDS due to their gelling ability, mucoadhesive property, colonic digestibility, and anticancer activity. Polymer mucoadhesion is augmentable by thiolation, e.g. pectin to thiolated pectin (TP). Meanwhile, P-CS polyelectrolyte complex has been shown to improve structural stability. Herein, we fabricated, characterized, and evaluated 5-fluorouracil-loaded primary DDS combining TP and CS as a composite (TPCF) through triple crosslinking actions (calcium pectinate, polyelectrolyte complex, disulfide). Combination of these crosslinking yields superior mucoadhesion property relative to single- or dual-crosslinked counterparts, with comparable drug release profile and drug compatibility. PCF and TPCF exhibited targeted cytotoxicity towards HT29 CRC cells with milder cytotoxicity towards HEK293 normal cells. In conclusion, TP-CS composites are promising next-generation mucoadhesive and selectively cytotoxic biomaterials for CRC-targeted DDS.