Oleanolic acid loaded PEGylated PLA and PLGA nanoparticles with enhanced cytotoxic activity against cancer cells

Abstract

Oleanolic acid (OA) is a natural triterpenoid with anticancer properties, but its hydrophobic nature and poor aqueous solubility pose challenges in pharmaceutical formulation development. The present study aimed at developing OA-loaded mPEG-PLGA or mPEG-PLA nanoparticles (NPs) to improve the delivery of OA. The NPs were prepared by nanoprecipitation, and their physicochemical properties were characterized. The OA encapsulation efficiency of the NPs was between 40 and 75%. The size of the OA-loaded NPs was around 200-250 nm, which fell within the range required for tumor targeting by means of the enhanced permeability and retention (EPR) effect, and the negatively charged NPs remained physically stable for over 20 weeks with no aggregation observed. The OA-loaded NPs produced significant cytotoxic effects through apoptosis in cancer cell lines. Overall, the OA-loaded mPEG-PLGA NPs and mPEG-PLA NPs shared similar physicochemical properties. The former, especially the OA-loaded mPEG-P(D,L)LGA NPs, were more cytotoxic to cancer cells and therefore were more efficient for OA delivery. © 2015 American Chemical Society.