|Antitumor efficacy of a novel CLA-PTX microemulsion against brain tumors: in vitro and in vivo findings|
|Li, Dan1; Yang, Ke1; Li, Jie-Si1; Ke, Xi-Yu1; Duan, Yu1; Du, Ruo1; Song, Ping1; Yu, Ke-Fu1; Ren, Wei1; Huang, Dan1; Li, Xing-Huo1; Hu, Xin1; Zhang, Xuan1; Zhang, Qiang1,2|
|关键词||Cla-ptx Microemulsion Pharmacokinetics Brain Tumor Antitumor Efficacy Safety|
|刊名||INTERNATIONAL JOURNAL OF NANOMEDICINE|
|WOS标题词||Science & Technology|
|类目[WOS]||Nanoscience & Nanotechnology ; Pharmacology & Pharmacy|
|研究领域[WOS]||Science & Technology - Other Topics ; Pharmacology & Pharmacy|
|关键词[WOS]||CONJUGATED LINOLEIC-ACID ; BREAST-CANCER CELLS ; DRUG-DELIVERY SYSTEM ; WATER-SOLUBLE DRUGS ; NANOEMULSION FORMULATIONS ; ORAL BIOAVAILABILITY ; INTRANASAL DELIVERY ; LIPID NANOPARTICLES ; SOLID DISPERSION ; PACLITAXEL|
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 IC50 of the CLA-PTX microemulsion was 1.61 +/- 0.83 mu M 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 (R) 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 LD50 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.
|项目编号||81172992 ; 2009CB930300 ; 2013CB932501 ; BMU20110263|
|资助机构||National Natural Science Foundation of China ; National Basic Research Program of China (973 Program) ; Innovation Team of the Ministry of Education|
|作者单位||1.Peking Univ, Sch Pharmaceut Sci, Dept Pharmaceut, Beijing 100191, Peoples R China|
2.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
|Li, Dan,Yang, Ke,Li, Jie-Si,et al. Antitumor efficacy of a novel CLA-PTX microemulsion against brain tumors: in vitro and in vivo findings[J]. INTERNATIONAL JOURNAL OF NANOMEDICINE,2012,7:6105-6114.|
|APA||Li, Dan.,Yang, Ke.,Li, Jie-Si.,Ke, Xi-Yu.,Duan, Yu.,...&Zhang, Qiang.(2012).Antitumor efficacy of a novel CLA-PTX microemulsion against brain tumors: in vitro and in vivo findings.INTERNATIONAL JOURNAL OF NANOMEDICINE,7,6105-6114.|
|MLA||Li, Dan,et al."Antitumor efficacy of a novel CLA-PTX microemulsion against brain tumors: in vitro and in vivo findings".INTERNATIONAL JOURNAL OF NANOMEDICINE 7(2012):6105-6114.|