ROS-responsive nucleobase conjugated chitosan: Synthesis and evaluations for biomedical applications

Herein, chitosan has been functionalized with four nucleobases to investigate its mucoadhesive properties in the hydrogel form. These nucleobase-modified polymers were characterized by NMR, FT-IR, EDAX, TGA and evaluated for its ROS responsive degradation, cytocompatibility, mucoadhesion, hemocompatibility, anti-bacterial, anti-fungal and biofilm inhibitory properties. All the conjugated polymers have shown superior mucoadhesion along with the cyto- and hemo- compatibility as compared to chitosan. These functionalized polymers have shown excellent anti-bacterial activity against E. coli and S. aureus. In particular, the guanine-conjugated polymer (P4) showcased excellent mucoadhesive properties. This finding corroborated the in-silico prediction of the interaction of chitosan and conjugated chitosan polymers with the mucin. All modified chitosans possess potent anti-fungal activity for Candida albicans, Candida tropicalis and Candida glabrata along with the anti-biofilm properties for Candida tropicalis. P4 was found to reduce the multilayer polymicrobial biofilms consisting of bacterial and fungal species to a single layer. In addition, P4 as hydrogel scaffold has demonstrated excellent mucoadhesion and tissue adhesion. P4 hydrogel was found to release the anti-inflammatory drug diclofenac in ROS responsive manner. Hydrogel P4 displayed effectiveness in oral wound healing properties in-vivo in the case of an oral mucositis rat model.