Development of a Chitosan-Based Smart Hydrogel Composite as a Controlled Release Drug Delivery Agent

This work aims to develop a sustained-release drug delivery agent for diclofenac sodium (Ds), an anti-inflammatory drug. For this purpose, a multifunctional hydrogel composite (CsP@Ag) was developed using a natural, biocompatible polymer, chitosan (Cs) as a base polymer, 2,6-pyridinedicarboxaldehyde as a bifunctional cross-linker, and silver nitrate (AgNO₃), to enhance the structural properties. The reaction proceeds via Schiff base condensation, which was confirmed by the primary characterization techniques. The resulting hydrogel composite exhibits a honeycomb-like porous morphology, with a mesoporous structure and an average pore diameter of 38.8 nm. The physicochemical characterization validated the successful formation of CsP@Ag, and the enhancement in the thermomechanical properties by incorporation of AgNO₃ was also confirmed. Notably, CsP@Ag exhibits temperature-dependent swelling and pronounced pH responsiveness, achieving maximum swelling (4268%) at neutral pH. These stimuli-responsive properties enabled efficient drug loading and tailored release behavior. Ds was loaded at alkaline pH, in view of its solubility profile, while the <i>in vitro</i> drug release was performed at physiological pH. The kinetics demonstrated a sustained and controlled release behavior, and the results fit the Korsmeyer-Peppas model. The designed drug delivery system was subjected to cytotoxicity and biocompatibility tests as well. Overall, the prominent properties of CsP@Ag, like environmental responsiveness, prolonged release performance, and biocompatibility, offer the promising potential for advanced therapeutic applications.