ROS-responsive nucleobase conjugated chitosan: Synthesis and evaluations for biomedical applications
Neeraj Kulkarni, Govinda Shivaji Jadhav, Pranav Ravindra Kombe, Bhaskar Dewangan, Cherukuri Venkata Apparao, Srimanta Patra, Akash P. Sakla, Sapan Borah, Bichismita Sahu
Abstract
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.