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

Dan Li,1 Ke Yang,1 Jie-Si Li,1 Xi-Yu Ke,1 Yu Duan,1 Ruo Du,1 Ping Song,1 Ke-Fu Yu,1 Wei Ren,1 Dan Huang,1 Xing-Huo Li,1 Xin Hu,1 Xuan Zhang,1 Qiang Zhang1,21Department of Pharmaceutics, 2State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beiji...

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Autores principales:	Li D, Yang K, Li JS, Ke XY, Duan Y, Du R, Song P, Yu KF, Ren W, Huang D, Li XH, Hu X, Zhang X, Zhang Q
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/9000c396e68f469ca0d35ad6da5daa88
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spelling	oai:doaj.org-article:9000c396e68f469ca0d35ad6da5daa882021-12-02T01:07:53ZAntitumor efficacy of a novel CLA-PTX microemulsion against brain tumors: in vitro and in vivo findings1176-91141178-2013https://doaj.org/article/9000c396e68f469ca0d35ad6da5daa882012-12-01T00:00:00Zhttp://www.dovepress.com/antitumor-efficacy-of-a-novel-cla-ptx-microemulsion-against-brain-tumo-a11766https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Dan Li,1 Ke Yang,1 Jie-Si Li,1 Xi-Yu Ke,1 Yu Duan,1 Ruo Du,1 Ping Song,1 Ke-Fu Yu,1 Wei Ren,1 Dan Huang,1 Xing-Huo Li,1 Xin Hu,1 Xuan Zhang,1 Qiang Zhang1,21Department of Pharmaceutics, 2State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, ChinaBackground: Considering the observations that linoleic acid conjugated with paclitaxel (CLA-PTX) possesses antitumor activity against brain tumors, is able to cross the blood&ndash;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 &plusmn; 0.8 nm and the polydispersity index was 0.294 &plusmn; 0.024. In vitro cytotoxicity results showed that the IC50 of the CLA-PTX microemulsion was 1.61 &plusmn; 0.83 &micro;M for a C6 glioma cell line, which was similar to that of free paclitaxel and CLA-PTX solution (P &gt; 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&reg; 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.Keywords: CLA-PTX, microemulsion, pharmacokinetics, brain tumor, antitumor efficacy, safetyLi DYang KLi JSKe XYDuan YDu RSong PYu KFRen WHuang DLi XHHu XZhang XZhang QDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 6105-6114 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Li D Yang K Li JS Ke XY Duan Y Du R Song P Yu KF Ren W Huang D Li XH Hu X Zhang X Zhang Q Antitumor efficacy of a novel CLA-PTX microemulsion against brain tumors: in vitro and in vivo findings
description	Dan Li,1 Ke Yang,1 Jie-Si Li,1 Xi-Yu Ke,1 Yu Duan,1 Ruo Du,1 Ping Song,1 Ke-Fu Yu,1 Wei Ren,1 Dan Huang,1 Xing-Huo Li,1 Xin Hu,1 Xuan Zhang,1 Qiang Zhang1,21Department of Pharmaceutics, 2State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, ChinaBackground: Considering the observations that linoleic acid conjugated with paclitaxel (CLA-PTX) possesses antitumor activity against brain tumors, is able to cross the blood&ndash;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 &plusmn; 0.8 nm and the polydispersity index was 0.294 &plusmn; 0.024. In vitro cytotoxicity results showed that the IC50 of the CLA-PTX microemulsion was 1.61 &plusmn; 0.83 &micro;M for a C6 glioma cell line, which was similar to that of free paclitaxel and CLA-PTX solution (P &gt; 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&reg; 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.Keywords: CLA-PTX, microemulsion, pharmacokinetics, brain tumor, antitumor efficacy, safety
format	article
author	Li D Yang K Li JS Ke XY Duan Y Du R Song P Yu KF Ren W Huang D Li XH Hu X Zhang X Zhang Q
author_facet	Li D Yang K Li JS Ke XY Duan Y Du R Song P Yu KF Ren W Huang D Li XH Hu X Zhang X Zhang Q
author_sort	Li D
title	Antitumor efficacy of a novel CLA-PTX microemulsion against brain tumors: in vitro and in vivo findings
title_short	Antitumor efficacy of a novel CLA-PTX microemulsion against brain tumors: in vitro and in vivo findings
title_full	Antitumor efficacy of a novel CLA-PTX microemulsion against brain tumors: in vitro and in vivo findings
title_fullStr	Antitumor efficacy of a novel CLA-PTX microemulsion against brain tumors: in vitro and in vivo findings
title_full_unstemmed	Antitumor efficacy of a novel CLA-PTX microemulsion against brain tumors: in vitro and in vivo findings
title_sort	antitumor efficacy of a novel cla-ptx microemulsion against brain tumors: in vitro and in vivo findings
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/9000c396e68f469ca0d35ad6da5daa88
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Antitumor efficacy of a novel CLA-PTX microemulsion against brain tumors: in vitro and in vivo findings

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