Hybrid nanocarrier system for guiding and augmenting simvastatin cytotoxic activity against prostate cancer

Abstract

Prostate cancer is the most common non-skin cancer among men. Though statins are mainly used as antihyperlipidemic drugs, many studies have reported their proapoptotic and antimetastatic activities on prostate cancer. However, the poor solubility and insufficient delivery of statins in tumor site limit their anticancer activity. The present study introduces an efficient hybrid drug delivery system for the treatment of prostate cancer. The system involves the chemical conjugation of Simvastatin (SMV), a statin compound, to acid-terminated poly(D, L-lactic-co-glycolic acid), PLGA chains followed by its conversion into nanoparticles (NPs), with in situ physical incorporation of more SMV and superparamagnetic iron oxide nanoparticles (SPIONS) into the PLGA NPs. The PLGA-based hybrid nanocarrier system has been designed in such a way to evade the low bioavailability of SMV, confer sustained release of both encapsulated and chemically conjugated SMV, as well as enhancing the anti-cancer effect of the formula via the magnetic targeting with the aid of the encapsulated SPIONS. Magnetism, morphological and physicochemical characterizations, as well as in-vitro release studies were performed. Besides, cytotoxicity on human prostate cancer cell line (PC-3) was evaluated using MTT assay, cell cycle arrest analysis, annexin V/propidium iodide apoptosis assay and ELISA immunoassay for apoptotic enzyme. Optimum PLGA-based hybrid nanocarrier significantly improved the SMV anticancer activity against human prostate cancer cell line through both apoptosis mechanism and retardation of G2-M phase of cell cycle. Also, the up-regulation of the Caspase 3 was aligned with cytotoxicity study’s findings.