Investigation of the effect of encapsulating cisplatin with the active compound silibinin in PLGA polymeric nanoparticles on the HeLa cervical cancer cell line
Cisplatin remains one of the most widely used chemotherapeutic agents, yet its clinical efficacy is limited by poor tumor selectivity, dose-dependent toxicity, and the development of resistance. Silibinin, a hydrophobic natural compound with antioxidant and anticancer activity, has been proposed as a complementary agent capable of enhancing therapeutic responses. In this study, poly(lactic-co-glycolic acid) (PLGA) nanoparticles were developed to encapsulate cisplatin and silibinin individually, aiming to improve their stability, sustain release, and enhance cytotoxic activity against HeLa cervical cancer cells. Nanoparticles were synthesized using a modified double-emulsion (W/O/W) solvent evaporation method and characterized for particle size, zeta potential, morphology, encapsulation efficiency, and in vitro release. Silibinin-loaded nanoparticles (F4) and cisplatin-loaded nanoparticles (F7) demonstrated optimal physicochemical properties, with encapsulation efficiencies of 81.2% and 59.4%, respectively. TEM imaging confirmed spherical morphology, and DLS analysis showed particle sizes of 144 nm (silibinin) and 164 nm (cisplatin). In vitro drug release studies performed under physiological (pH 7.4, 37 °C) and tumor-mimicking conditions (pH 5.2, 42 °C) revealed accelerated release at acidic and hyperthermic conditions. Silibinin release increased from 53.77% to 81.95%, while cisplatin release increased from 57.18% to 73.41% under tumor-like conditions. Both formulations exhibited biphasic release behavior consistent with diffusion-controlled kinetics. Cytotoxicity assessment using the MTT assay demonstrated a significant reduction in HeLa cell viability for both optimized formulations, with the combined treatment showing enhanced inhibitory effects compared to individual drugs. Overall, the findings indicate that PLGA nanoparticles can effectively enhance the controlled release and anticancer activity of cisplatin and silibinin, supporting their potential application as a more efficient and less toxic therapeutic strategy for cervical cancer.