Self-assembled sustainable bionanocomposite hydrogels from chitosan for the combination chemotherapy of hydrophobic and hydrophilic drugs.

Self-assembled hydrogels derived from naturally sourced polymers have gained significant interest in drug delivery applications, owing to their potential, exceptional biocompatibility and sustainable properties. This work presents the development and application of self-assembled nanocomposite hydrogels from chitosan and nanosilver as a pH responsive drug delivery system for the controlled release of doxorubicin and paclitaxel in anticancer therapy. Chitosan was functionalized with 4-formyl benzoic acid for incorporating both hydrophobic and hydrophilic anticancer drugs. The self-assembled nanocomposite hydrogels formed from chitosan and 4-formyl benzoic acid by various non-covalent interactions were studied by FT-IR, Dynamic Light Scattering (DLS), and rheology analysis. Rheology studies demonstrated the hydrogel's shear-thinning nature, enabling easy injection. The antibacterial activity can be evidenced by agar-well diffusion assay and MIC values were measured. The antibacterial effect was analyzed by agar-well diffusion assays and H-DCFDA assay, providing a comprehensive understanding. In-vivo pharmacokinetic studies on Wistar rats demonstrated promising and effective systemic circulation of drug loaded material in blood, thus supporting its potential for therapeutic applications. All these studies and results demonstrates feasibility and a novel synergistic dual drug delivery approach, promising the synergy between hydrophobic paclitaxel (PTX) and hydrophilic Doxorubicin hydrochloride (Dox.HCl), for improved anticancer efficacy.