Formulating etoposide in a nanoemulsion containing polyunsaturated fatty acids potentiates its anti-proliferation and anti-invasion activities against the ovarian cancer cells

Abstract

Incorporation of etoposide (ETP) into nanoemulsion (NE) containing polyunsaturated fatty acids (PUFAs) may potentially augment its antiproliferation effect on the cancer cells. The current study aimed to examine the <i>in vitro</i> antitumor activity of a novel formulation (ETP-BC/EP-NE) produced by combining the anticancer drug (ETP) with NE (BC/EP-NE) consisting of the black currant seed and organic evening primrose oils. The produced formulas were physically characterized using zetasizer measurements. Their cytotoxic effect was testified at concentrations ranges from 0.0001 to 5 μM using CCK-8. Apoptotic and anti-invasion effects were evaluated using the assays of mitochondrial membrane potential, annexin V-FITC double staining, DNA fragmentation, and collagen-based cell invasion. According to the zetasizer characterization, the nano-suspensions of ETP-BC/EP-NE have z-average diameters of 87.63 ± 3.30 nm with an average surface zeta potential of −0.605 ± 0.003 mV. A reduction of 50% in the growth of SK-OV-3 cells was found at a distinctly lower concentration of ETP-BC/EP-NE (IC₅₀ = 0.04 ± 0.2 μM) than that of ETP (IC₅₀ = 4.75 ± 0.1 μM). Results indicated that ETP-BC/EP-NE had a greater apoptotic effect than ETP on SK-OV-3 cells, which was attributed to the larger amount of late apoptotic cells (41.9 ± 1.05%), higher loss of mitochondrial membrane potential, and more intensive fragmented DNA. The ETP-BC/EP-NE treatment suppressed the cellular invasion by 55%, whereas ETP impeded the cellular invasion by only 3%. Formulating ETP with PUFAs in NE had ameliorated the efficacy of ETP.