Polyalthic Acid in Polymeric Nanoparticles Causes Selective Growth Inhibition and Genotoxicity in MCF-7 Cells

Polyalthic acid (PA) is a diterpene present in several trees of the Copaifera genus, with reported antitumor activity but poor water solubility. The aim of this work was the incorporation of PA in polymeric nanoparticles and the evaluation of the antiproliferative activity of this formulation in tumor (MCF-7) and normal (MCF-10A) breast cell lines. The nanoparticles were obtained by nanoprecipitation, using poly lactic-co-glycolic acid (PLGA) as the main material. Scanning electron microscopy showed nanoparticles with semispherical morphology, and dynamic light scattering measures revealed negative surface charge and average size of 98.64 +/- 28 nm. The encapsulation efficiency was 98% and the drug loading was 15.6% +/- 0.02%. Treatments with PA nanoparticles reduced cell proliferation more efficiently than free PA and the effect was selective on MCF-7 cells. Comet assay revealed a selective DNA damage induction by the nanoformulation on the tumor cells, which probably caused the antiproliferative effect. Our results show that PA incorporated in PLGA nanoparticles has potential as a selective cytostatic and genotoxic agent against MCF-7 cells. (AU)