Topotecan Incorporation Into Avocado Oil-based Nanoemulsion Potentiates Its Inhibitory Effect on the Cellular Growth of Various Human Cancer Cells

Abstract Background: The aim is to ameliorate the anticancer activity of topotecan (topoisomerase [TOPO]) by solubilizing it in a nanoemulsion (NE) delivery system containing avocado oil (AO), then to assess its cytotoxicity in MCF-7 breast, HCT116 colon, HeLa cervical, and HepG2 liver cancer cells. Methods: AO-NE formulation was developed using an ultrasonic homogenizer and characterized by a zeta-sizer and transmission electron microscope (TEM). The effects of the TOPO-AO-NE formula on viability, cellular and nuclear morphology of cancer cells, as well as TOPO cellular accumulation, inflammatory effects, apoptosis, and autophagy, were examined. Results: The nanosized particles of the AO-NE formula were negatively charged (114.83 ± 1.10 nm, −8.96 ± 0.14 mV) even after TOPO loading (75.44 ± 8.51 nm,−5.79 ± 0.38 mV). In contrast to free TOPO, TOPO-AO-NE exhibited significant anti-proliferation, clear apoptotic changes, improved TOPO cellular uptake and decreased IC 50 from (12.65 ± 0.05, 15.78 ± 0.08, 26.82 ± 0.50, and 5.50 ± 0.50 μM) to (2.35 ± 0.05, 4.90 ± 0.05, 2.58 ± 0.08, and 4.87 ± 0.08 μM) in MCF-7, HCT116, HeLa, and HepG2 cells, respectively. In MCF-7 and HCT116 cells, cytotoxicity of TOPO-AO-NE was attributed to decreased IL-6 levels relative to a negative control, lessened autophagic LC-3 levels compared to free TOPO-treated cells, and induction of type-I apoptotic cell death. In HeLa cells, TOPO-AO-NE-induced apoptosis through autophagy inhibition and induction of type-I apoptosis. In HepG2 cells, AO-NE reduced IL-6 cytokines and induced both type-I-apoptotic and type-II-autophagic cell deaths in comparison with control cells. Conclusion: Loading TOPO in AO-NE has dramatically enhanced its’ antiproliferative effects in cancer cells.