Design of Chitosan‐Piperazinyl‐Tannic Acid‐Metal Oxide Composites for Controlled Release of Norfloxacin and Curcumin: Evaluation of Antibacterial and Cytotoxicity Activities

ABSTRACT

Novel chitosan‐tannic acid conjugate crosslinked using piperazine‐1,4‐dicarbaldehyde (CS‐PIP‐TA) was synthesized and employed as a multifunctional platform to prepare ZnO‐ and CuO‐based composites for drug delivery and biological uses. Curcumin (CUR), norfloxacin (NOR), and dual CUR/NOR drug systems were loaded into CS‐PIP‐TA‐ZnO and CS‐PIP‐TA‐CuO composites, reaching loading efficiencies up to 98%. Structural characterization and physicochemical properties through FT‐IR, ¹ H‐NMR, TGA, XRD, EDX, SEM, and zeta potential analyses verified successful functionalization, metal oxide incorporation, and drug immobilization inside the polymeric matrix. SEM images showed greater surface roughness after metal oxide incorporation and drug encapsulation, whereas zeta potential findings pointed to moderate colloidal stability. In vitro release studies at pH 5.3 and 7.4 demonstrated sustained release of CUR and NOR over prolonged periods, exceeding 900 h for some formulations. Drug release followed zero‐order or Higuchi kinetics, with predominantly Fickian diffusion behavior. The composites exhibited remarkable antibacterial activity against Gram‐positive and Gram‐negative bacteria, particularly the ZnO‐containing systems. Cytotoxicity studies demonstrated that ZnO‐based formulations, CS‐PIP‐TA‐ZnO@NOR and CS‐PIP‐TA‐ZnO@CUR/NOR, possessed significant anticancer activity against HepG‐2, MCF‐7, HCT‐116, and PC‐3 cell lines with lower toxicity toward normal WISH cells. Results indicate that the developed composites are promising multifunctional carriers for sustained drug delivery, antibacterial treatment, and anticancer therapy.