Enhancement of Efficacy and Reduced Toxicity of Cisplatin Through Self Nanoemulsifying Drug Delivery System (SNEDDS)
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 kgG 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 ratʼs 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…
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