Cyclodextrin modified biocompatible Chitosan-Cinnamaldehyde Schiff base hydrogels: Their antibacterial, antioxidant, and drug delivery potential

Chitosan (CS)-based hydrogels are promising platforms for drug delivery owing to their biocompatibility , biodegradability, and functional versatility. However, pure CS Schiff base hydrogels lack mechanical strength and rely on toxic cross-linkers, necessitating bio-safe alternatives viz. Cinnamaldehyde (CA). In this study, hybrid Chitosan-Cinnamaldehyde (CSCA) and Chitosan-Cinnamaldehyde-γ-Cyclodextrin (CSCDCA) hydrogels were synthesized to address the limitations. Encapsulation of CA into γ-Cyclodextrin (γ-CD) enhanced the stability of CA through the formation of an inclusion complex (IC), as confirmed by NMR analysis. CSCDCA hydrogels although relatively weaker, exhibited superior swelling/water retention capability over CSCA hydrogels. The release behavior of Rifampicin (Rif) a model hydrophobic drug, was monitored in both hydrogels. CSCDCA hydrogel showed more controlled release (∼56 % at pH 2 and 39 % at pH 7.4 over 30 h) compared to CSCA (∼70 % at pH 2 and 36 % at pH 7.4). Kinetic analysis indicated combined diffusion and relaxation mechanism of release. Antibacterial and antioxidant (AOX) activities confirmed significant activity, with CSCDCA achieving 95 % cell viability against human embryonic kidney (HEK-293) cells. These findings underscore the hydrogel's suitability as pH-sensitive drug delivery system (DDS), enhancing Rif's bioavailability, minimizing side effects , and establishing a benchmark for eco-friendly hydrogels in therapeutic applications. • Chitosan- Cinnamaldehyde hydrogels were synthesized via Schiff base reaction with bio-safe Cinnamaldehyde in γ-Cyclodextrin. • Hydrogels exhibited sustained release of Rifampicin, overcoming its poor solubility and bioavailability limitations. • Encapsulation of Cinnamaldehyde in γ-Cyclodextrin enhanced hydrogel stability, swelling and water retention properties. • The hydrogels showed significant antibacterial and antioxidant properties, indicating potential for biomedical applications. • Excellent biocompatibility with HEK-293 cells was observed, supporting their safe biomedical use.