Antitumor efficacy of a novel CLA-PTX microemulsion against brain tumors: in vitro and in vivo findings

نویسندگان

  • Dan Li
  • Ke Yang
  • Jie-Si Li
  • Xi-Yu Ke
  • Yu Duan
  • Ruo Du
  • Ping Song
  • Ke-Fu Yu
  • Wei Ren
  • Dan Huang
  • Xing-Huo Li
  • Xin Hu
  • Xuan Zhang
  • Qiang Zhang
چکیده

BACKGROUND Considering the observations that linoleic acid conjugated with paclitaxel (CLA-PTX) possesses antitumor activity against brain tumors, is able to cross the blood-brain barrier, but has poor water solubility, the purpose of this study was to prepare a novel CLA-PTX microemulsion and evaluate its activity against brain tumors in vitro and in vivo. METHODS The in vitro cytotoxicity of a CLA-PTX microemulsion was investigated in C6 glioma cells. The in vivo antitumor activity of the CLA-PTX microemulsion was evaluated in tumor-bearing nude mice and rats. The pharmacokinetics of the CLA-PTX microemulsion were investigated in rats, and its safety was also evaluated in mice. RESULTS The average droplet size of the CLA-PTX microemulsion was approximately 176.3 ± 0.8 nm and the polydispersity index was 0.294 ± 0.024. In vitro cytotoxicity results showed that the IC(50) of the CLA-PTX microemulsion was 1.61 ± 0.83 μM for a C6 glioma cell line, which was similar to that of free paclitaxel and CLA-PTX solution (P > 0.05). The antitumor activity of the CLA-PTX microemulsion against brain tumors was confirmed in our in vivo C6 glioma tumor-bearing nude mice as well as in a rat model. In contrast, Taxol(®) had almost no significant antitumor effect in C6 glioma tumor-bearing rats, but could markedly inhibit growth of C6 tumors in C6 glioma tumor-bearing nude mice. The pharmacokinetic results indicated that CLA-PTX in solution has a much longer circulation time and produces higher drug plasma concentrations compared with the CLA-PTX microemulsion. The results of the acute toxicity study showed that the LD(50) of CLA-PTX solution was 103.9 mg/kg. In contrast, the CLA-PTX microemulsion was well tolerated in mice when administered at doses up to 200 mg/kg. CONCLUSION CLA-PTX microemulsion is a novel formulation with significant antitumor efficacy in the treatment of brain tumors, and is safer than CLA-PTX solution.

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عنوان ژورنال:

دوره 7  شماره 

صفحات  -

تاریخ انتشار 2012