Abstract
To incorporate the topoisomerase I inhibitor, topotecan (TOPO), into oil-in-water nanoemulsion delivery system based on sesame oil (SO-NE), with the aim to enhance its anti-proliferative effect on MCF-7 breast, HCT116 colon, HeLa cervical, and HepG2 liver cancer cells.
SO-NE was formulated by mixing different volume fractions of SO (3%), Tween 80 (10%), Span 20 (5%), and water (82%) using the high-pressure ultrasonication technique. SO-NE and TOPO-loaded SO-NE (TOPO–SO–NE) were physically characterized by zeta sizer and transmission electron microscope. The in vitro drug release of TOPO–SO–NE relative to the free TOPO solution was assessed by the dialysis bag technique. The cytotoxicity of the TOPO–SO–NE formula was determined in vitro using crystal violet assay. DAPI fluorescent stains were used for cellular morphology and death assessments. Additionally, TOPO cellular uptake and inflammatory effect after TOPO loading into SO-NE formula were determined.
SO-NE formula was found to have negatively charged nanosized particles even after TOPO loading (Z-diameter = 73.66 ± 5.5 nm, Zetapotential = −7.63 ± 0.24 mV). In addition, TOPO–SO–NE formulation exhibited a beneficial TOPO prolonged and sustained release over 24 h. In all tested cell lines, TOPO–SO–NE formula exhibited considerable anti-proliferation effect with decreased IC50 and caused distinct apoptotic changes in cancer cells, which was evidenced by the enhanced cellular uptake of TOPO. The concentrations of interlukin-6 (IL-6), an inflammatory marker, in MCF-7, HCT116 and HepG2 cells were suppressed by TOPO–SO–NE treatment, but they got reversed in HeLa cells.
Incorporation of TOPO into SO-NE has remarkably improved its cytotoxicity in MCF-7, HCT116, HeLa and HepG2 cancer cells. The mechanisms of cell death were through the induction of apoptosis, enhancement of TOPO cellular accumulation ratios and affecting the inflammatory agent, interlukin-6 (IL-6), concentrations.
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•An oil-in-water nanoemulsion based on sesame oil (SO-NE) was formulated.•SO-NE consisted of sesame oil, tween 80, Span 20 and water.•Remarkable enhancement of topotecan antitumor activity when loaded in SO-NE.•Incorporation of topotecan in SO-NE increased its accumulation in the cancer cells.•TOPO–SO–NE reduced inflammation in MCF-7, HCT116 and HepG2 cancer cells.