Abstract
Background and Objective: Statins are antihyperlipidemic drugs which reported with its high cytotoxicity. Micelles are identified for their potential in drug delivery of cytotoxic agents. Thus, the purpose of this study was to determine the potential enhancement of simvastatin cytotoxicity activity in MCF-7 breast cancer cells via its formulation in micelles. Materials and Methods: Simvastatin was formulated in micelles using a thin-film hydration technique. Particle size, shape, and release studies were used to characterize the formula. Results: Simvastatin micelles exhibited enhanced in vitro drug release. Further, it exhibited enhanced cytotoxicity against breast cancer cells. Cell cycle analysis indicated the accumulation of cells challenged with simvastatin micelles in G2/M and pre-G1 phases. Staining of cells with annexin V indicated a significant elevation of percentage cells with early and late apoptosis as well as total cell death. Besides, the formulation significantly disturbed mitochondrial membrane potential and cellular content of caspase 3. Besides, the intracellular release of Reactive Oxygen Species (ROS) was enhanced by simvastatin micelles. Conclusion: The prepared formula of simvastatin significantly potentiates its cytotoxic activities against MCF-7cells. This is mediated, at least partly, by enhanced simvastatin cellular permeation and apoptosis.