Gemcitabine-Loaded Poly (HEMA-co-Acrylic Acid-co-Maleic Acid) Bentonite Hydrogels: Physicochemical Characterisation and in Vitro Drug Release

Abstract

Polymeric composite hydrogel particles incorporating inorganic nanoclays, such as bentonite, have recently received increasing attention as versatile platforms for controlled drug delivery due to their enhanced structural stability and tunable swelling behavior. In this study, a pH-responsive Poly (2-hydroxyethyl methacrylate) -co-acrylic acid-co-maleic acid) bentonite (HEMAPAM-Bentonite) nanocomposite hydrogel was developed as a carrier system for Gemcitabine (GEM) to improve its therapeutic efficacy in the treatment of ovarian cancer. The synthesized nanocomposite was characterized using Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), zeta potential analysis, and X-ray diffraction (XRD). Physicochemical characterisation of the dispersed composite hydrogel particles revealed an average hydrodynamic diameter of 1135 nm with a narrow polydispersity index (PDI) of 0.3, and a zeta potential of -14.4 mV. The optimised triple-terpolymer matrix achieved an exceptionally high Gemcitabine loading efficiency of 90.3%. Furthermore, the system exhibited pronounced pH-dependent swelling (reaching maximum swelling ratios of approximately 297% and 339% at pH 5.5 and 7.4, respectively), thereby enabling a controlled, biphasic drug-release profile. Swelling behavior, drug loading efficiency, and in vitro release profiles were systematically evaluated under physiological (pH 7.4) and acidic (pH 5.5) conditions. The system exhibited high drug-loading efficiency (~ 90%) and pronounced pH-dependent swelling, enabling a controlled, biphasic release profile. Furthermore, cytotoxicity studies on SKOV3 ovarian cancer cells demonstrated fair biocompatibility of the blank composite hydrogel particles, while the GEM-loaded formulation showed enhanced, time-dependent anticancer activity compared to free Gemcitabine. These findings suggest that the developed bentonite-based nanocomposite hydrogel particle system represents a promising and effective platform for controlled delivery of chemotherapeutic agents in cancer therapy.