Green synthesis of PLGA and fabrication of topotecan and thymoquinone dual anticancer drug loaded PLGA nanoparticles: a controlled release study for cancer therapy

Cancer therapy is often hindered by poor solubility, low bioavailability, drug resistance, and tumor microenvironmental barriers associated with conventional chemotherapeutics. Polymeric nano–drug delivery systems offer a promising strategy to overcome these limitations, particularly for synergistic multi-drug delivery. In this study, a biodegradable and biocompatible PLGA copolymer (70:30, M̅w ≈ 14,500) was synthesized by ring-opening polymerization using zinc proline complex as an initiator through a green route. The copolymer’s potential for delivering topotecan (TPT), a water-soluble chemotherapeutic, thymoquinone (TQ), a poorly water-soluble chemotherapeutic, and their combination (TPT+TQ) for cancer treatment was investigated. These nanoparticles demonstrateda consistent particle size < 200 nm high encapsulation efficiency along with desirable controlled-release attributes. Moreover, they exhibited specific release characteristics and cytotoxic effects against HeLa cells, achieving an IC50 value of 20.88 µM for the combination therapy (TPT+TQ). Additionally, cytocompatibility testing on L929 fibroblasts confirmed over 98% cell viability for blank PLGA nanoparticles. Additionally, confocal imaging studies confirmed efficient cellular uptake and nuclear localization of the nanoparticles. Overall, the PLGA based dual drug loaded nanoparticles presents a promising approach for targeted, synergistic co-delivery, potentially improving efficacy and reducing toxicity in cancer therapy.