Nanomicellar formulation of clotrimazole improves its antitumor action toward human breast cancer cells

Abstract

Background: Although demonstrated as a selective anticancer drug, the clinical use of clotrimazole (CTZ) is limited due to its low solubility in hydrophilic fluids. Thus, we prepared a water-soluble nanomicellar formulation of CTZ ( n CTZ) and tested on the human breast cancer cell line MCF-7 biology. Methodology/Principal Findings: CTZ was nanoencapsulated in tween 80 micelles, which generated nanomicelles of, approximately, 17 nm of diameter. MCF-7 cells were treated withn CTZ and unencapsulated DMSO-solubilized drug ( s CTZ) was used for comparison. After treatment, the cells were evaluated in terms of metabolism, proliferation, survival and structure. We found that n CTZ was more efficient than s CTZ at inhibiting glycolytic and other cytosolic and mitochondrial enzymes. Moreover, this increased activity was also observed for lactate production, intracellular ATP content, ROS production and antioxidant potential. As a consequence, n CTZ-treated MCF-7 cells displayed alterations to the plasma membrane, mitochondria and the nucleus. Finally, n CTZ induced both apoptosis and necrosis in MCF-7 cells. Conclusions/Significance: MCF-7 cells are more sensible to n CTZ than to s CTZ. This was especially evident on regard to antioxidant potential, which is an important cell defense against drugs that affect cell metabolism. Moreover, this water-soluble formulation of CTZ strengths its potential use as an anticancer medicine.