A novel submicron emulsion system loaded with vincristine每oleic acid ion-pair complex with improved anticancer effect: in vitro and in vivo studies

作者：Zhang T; Zheng Y; Peng Q; Cao X; Gong T; Zhang ZR

来源：International Journal of Nanomedicine, 2013.

DOI：http://dx.doi.org/10.2147/IJN.S41775

• ion-pair complex
• submicron emulsion
• cytotoxicity
• apoptosis
• cell uptake

novel submicron emulsion system loaded with vincristine每oleic acid ion-pair complex with improved anticancer effect: in vitro and in vivo studies Original Research (95) Total Article Views Authors: Zhang T, Zheng Y, Peng Q, Cao X, Gong T, Zhang ZR Published Date March 2013 Volume 2013:8 Pages 1185 - 1196 DOI: http://dx.doi.org/10.2147/IJN.S41775 Received: 18 December 2012 Accepted: 02 February 2013 Published: 20 March 2013 Ting Zhang,1 Yong Zheng,2 iang Peng,3 Xi Cao,1 Tao Gong,1 Zhirong Zhang1 1Key Laboratory of Drug Targeting and Drug Delivery Systems, Sichuan University, Chengdu, People＊s Republic of China; 2Second Affiliated Hospital, Chongqing Medical University, Chongqing, People＊s Republic of China; 3State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, People＊s Republic of China Background: Vincristine (VCR), which is a widely used antineoplastic drug, was integrated with a submicron-emulsion drug-delivery system to enhance the anticancer effect. Methods: After the formation of a VCR每oleic acid ion-pair complex (VCR-OA), the VCR-OA-loaded submicron emulsion (VCR-OA-SME), prepared by classical high-pressure homogenization, was characterized and its in vitro anticancer effects were evaluated. Results: The submicron-emulsion formulation exhibited a homogeneous round shape. The mean particle size, zeta potential, and encapsulation efficiency were 157.6 ㊣ 12.6 nm, 26.5 ㊣ 5.0 mV and 78.64% ㊣ 3.44%, respectively. An in vitro release study of the VCR-OA-SME revealed that 12.4% of the VCR was released within the first 2 hours (initial burst-release phase) and the rest of the drug was detected in the subsequent sustained-release phase. Compared with VCR solution, the pharmacokinetic study of VCR-OA-SME showed relatively longer mean residence time (mean residence time [0每﹢] increased from 187.19 to 227.56 minutes), higher maximum concentration (from 252.13 ng/mL to 533.34 ng/mL), and greater area under the curve (area under the curve [0每﹢] from 11,417.77 米g/L/minute to 17,164.34 米g/L/minute. Moreover, the VCR-OA-SME exhibited higher cytotoxicity (P %26lt; 0.05) on tumor cells by inducing cell arrest in the G2/M phase or even apoptosis (P %26lt; 0.05). Conclusion: The VCR-OA-SME formulation in our study displayed great potential for an anticancer effect for VCR.

• 出版日期2013