Twin Screw Extrusion Mechanochemical Synthesis of Natural Copolymer Hydrogel: A Swell‐Controlled System for Stimuli‐Responsive Lornoxicam Delivery and In Vitro Cytocompatibility

ABSTRACT Recent advancements in the development of natural polymer hydrogels led to the exploration of the potential of gelatin (Gel) and tragacanth gum (TG) for the design of graphitic carbon nitride (g‐CN) impregnated copolymers (Gel/g‐CN/TG) via twin screw extrusion mechanochemical synthesis (TSE‐MS) approach for use in drug delivery. The copolymer hydrogel was confirmed by UV–vis spectroscopy, SEM, DLS, XRD, FTIR, zeta potential (ZP), and BET. The copolymer hydrogel offers a swell‐controlled drug‐delivery platform for lornoxicam (LXM), providing enhanced structural integrity and sustained drug release while facilitating favorable interactions with living cells (cytocompatibility). The Gel/g‐CN/TG hydrogel exhibited pH‐ and temperature‐responsive behavior, achieving a maximum LXM loading efficiency of 73.93% under the optimized loading condition (4 mg/mL LXM, pH 7.4), while 70.04% of the loaded LXM was cumulatively released after 24 h at pH 7.4 and 30°C. Release kinetics were best described by the Peppas–Sahlin model and indicated predominantly Fickian diffusion. As a result, the hydrogel is pH‐responsive and cytocompatible in vitro, serving as a suitable delivery platform for anti‐inflammatory drugs.