Novel pH-responsive folate conjugated chitosan and thiolated carboxymethyl cellulose based nanoparticles: potential approach for site-specific targeting in colon cancer treatment

The study objective was to develop folate decorated chitosan (CHT-FA) by the carbodiimide-mediated process to utilize the overexpressed folate receptors in the treatment of colon cancer. The substitution degree of FA to CHT was 1.4 %. FTIR and H¹NMR ensured the successful conjugation of FA with CHT. Thermal analysis and XRD demonstrated the thermal stability and amorphous nature of CHT-FA after conjugation. Thiolation of carboxymethyl cellulose, having a 1612.35 μmol/g thiol group, was achieved via oxidation followed by reductive amination. CHT-FA and thiolated carboxymethyl cellulose (CMC-SH) were utilized in the development of nanoparticles with eudragit S100 coating (EU-FU-CHT-FA/CMC-SH NPs) for targeted delivery to the colon. The fabricated NPs demonstrated a higher release pattern at 7.4 pH after <5 % release at 1.2 pH. CHT-FA/CMC-SH NPs showed enhanced mucoadhesion time by up to 237 min. Furthermore, compared to the FU solution, the MTT analysis showed that FU-CHT-FA/CMC-SH NPs had a more cytotoxic effect and increased cellular uptake in the Caco-2 cell line via the folate receptor-facilitated endocytosis process along with the consequence of thiolation which prevents closer of tight junction, resulting in enhanced cellular absorption. These findings support the potential of the developed NPs as a tumor-targeted therapeutic delivery.