Pharmacokinetic and in vitro cytotoxic evaluation of cholesterol-rich nanoemulsion of cholesteryl-succinyl-5-fluorouracil

In this study, in vitro cytotoxic effects and pharmacokinetic (PK) profile cholesterol-rich nanoemulsion (LDE) of cholesteryl-succinyl-5-fluorouracil (CS-5-FU) were investigated to improve therapeutic efficacy, bioavailability and to reduce adverse effects of the treatment. WE nanoemulsion of CS-5-FU was prepared by high energy emulsification technique, characterized and evaluated in terms of droplet size, polydispersity, zeta potential, viscosity, surface morphology, refractive index and drug release. Optimized LDE nanoemulsion presented significant cytotoxic effects in MDA-MB-231 breast cancer and LoVo colon cancer cells as compared to ethanolic solution of CS-5-FU (free CS-5-FU). PK studies in male Wistar rats showed that LDE nanoemulsion presented significant improvement in peak plasma concentration, area under curved and bioavailability profile of CS-5-FU as compared to ethanolic solution of CS-5-FU after intravenous bolus administration. The bioavailability of CS-5-FU was enhanced around two times by WE nanoemulsion with respect to its ethanolic solution. Overall, the results of this study indicated that developed LDE nanoemulsion could be used for chemoprevention of breast and colon cancers. (C) 2015 Elsevier B.V. All rights reserved.