Abstract
Background: Cisplatin is a potent antineoplastic agent with high therapeutic efficacy against many kinds of tumors. Its clinical use limited by its numerous side-effects, especially nephrotoxicity. Objective: The aim of this study was directed to formulate cisplatin self-nanoemulsifying drug delivery system (cisplatin-SNEDDS) as an attempt to improve the therapeutics activity and reduction of cisplatin toxicity. Materials and Methods: To evaluate these effects the cytotoxic activity of cisplatin-SNEDDS on the growth of Ehrlich Ascites Carcinoma (EAC) was assessed by determine the survival time of tumor-bearing mice, cisplatin cellular uptake, apoptosis induction, cell cycle distribution and renal function after treatment with cisplatin-SNDDS, compared with free cisplatin. Results: Free cisplatin increased the mean survival time of tumor bearing mice to 36 days compared with tumor bearing control mice while treatment of tumor bearing mice with cisplatin-SNEDDS showed a significant increase in their mean survival time to 44.30 days. Also, cisplatin-SNEDDS (7.5 mg kg(-1)) significantly accumulated the cells in sub-G(1) and dramatically increased the percentage of early apoptotic cells in comparison to free cisplatin. Treatment with cisplatin-SNEDD retained rat's serum urea, creatinine and TAC levels to normal level and significantly increase the reduced glutathione in kidney homogenate compared to animals treated with free cisplatin. Conclusion: The SNEDDS enhanced the cytotoxic activity of cisplatin against the growth of EAC in vivo and protect against its nephrotoxicity.