Abstract 4505: Preparation and anti-tumor growth of polyethylene glycol-poly lactic acid block copolymers sorafenib nanoparticles.

Abstract

Abstract BACKGROUND&AIMS: In vitro and in vivo studies have showed that sorafenib can inhibit the growth of liver cancer cells and solid tumor. However, poor water solubility, short half-life, high side-effect limit its clinical application in malignant tumor treatment. In this study, we report on the preparation of sorafenib nanoparticles by nanotechnology, and to observe the anti-hepatocarcinoma effect and in vivo metabolism of sorafenib nanoparticles. Methods:Polyethylene glycol-poly lactic acid block copolymers were synthesized with ring-opening polymerization technique as drug carrier material. Polyethylene glycol-poly lactic acid block copolymers sorafenib nanoparticles were prepared with nanometer precipitation method. The particle diameter and surface potential of sorafenib nanoparticles were determined by nanometer particle size and zeta otentiometer(Nano-ZS ZEN3600, Malvern). Drug-loading rate and entrapment rate were determined by ultraviolet spectrophotometer. In vitro slow release of sorafenib nanoparticles was determined by extracorporeal dialysis. The effect of sorafenib nanoparticles on H22 liver cancer cells proliferation was determined with CCK8 reagent in vitro culture .In vivo pharmacokinetics of sorafenib nanoparticles was analysed with DAS2.1.1 software. Results:Sorafenib nanoparticles were round, particle diameter was 127.3±2.0 nm, Zeta potential was -3.35±0.42 mV, drug-loading rate was 6.78%, entrapment rate was 98.21%. In vitro accumulative release rate of sorafenib nanoparticles at 24h, 48h, 72h, 96h were respectively 50.9073%, 56.2395%, 60.2561%, 63.2843%. The inhibitive effect of sorafenib nanoparticles on H22 liver cancer cells proliferation was more enhanced than that of sorafenib at the same drug concentration(F=74.988,P<0.05), The inhibitive effect of sorafenib nanoparticles on H22 liver cancer cells proliferation enhanced at the increase of sorafenib concentration. The in vivo metabolism time of sorafenib in sorafenib nanoparticles group was longer than that of sorafenib group (SNP t1/2, 13.95h vs S t1/2, 9.67h; t=2.618, P<0.05). Conclusion:Sorafenib nanoparticles can significantly inhibit the cells proliferation of liver cancer, and prolong in vivo metabolism of srafenib. The preparation of sorafenib nanoparticles has established good theoretical basis to further study in vivo anti-tumor effect and mechanism of sorafenib nanoparticles . Citation Format: Jianmin Qin. Preparation and anti-tumor growth of polyethylene glycol-poly lactic acid block copolymers sorafenib nanoparticles. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4505. doi:10.1158/1538-7445.AM2013-4505