In vitro and in vivo efficacy of edelfosine-loaded lipid nanoparticles against glioma

JOURNAL OF CONTROLLED RELEASE

卷:156

Article

de Mendoza, Ander Estella-Hermoso¹  Preart, Veronique²  Mollinedo, Faustino³  Blanco-Prieto, Maria J.¹ 

[1] Univ Navarra, Sch Pharm, Dept Pharm & Pharmaceut Technol, E-31080 Pamplona, Spain

[2] Catholic Univ Louvain, Louvain Drug Res Inst, B-1200 Brussels, Belgium

[3] Univ Salamanca, CSIC, Ctr Invest Canc, Inst Biol Mol & Celular Canc, E-37007 Salamanca, Spain

关键词: Edelfosine;    Glioma;    Lipid nanoparticles;   

DOI  :  10.1016/j.jconrel.2011.07.030

来源: Elsevier

【 摘 要 】

Edelfosine is the prototype molecule of a family of anticancer drugs collectively known as synthetic alkyl-lysophospholipids. This drug holds promise as a selective antitumor agent, and a number of preclinical assays are in progress. In this study, we observe the accumulation of edelfosine in brain tissue after its oral administration in Compritol (R) and Precirol (R) lipid nanoparticles (LN). The high accumulation of edelfosine in brain was due to the inhibition of P-glycoprotein by Tween (R) 80, as verified using a P-glycoprotein drug interaction assay. Moreover, these LN were tested in vitro against the C6 glioma cell line, which was later employed to establish an in vivo xenograft mouse model of glioma. In vitro studies revealed that edelfosine-loaded LN induced an antiproliferative effect in C6 glioma cell line. In addition, in vivo oral administration of drug-loaded LN in NMRI nude mice bearing a C6 glioma xenograft tumor induced a highly significant reduction in tumor growth (p<0.01) 14 days after the beginning of the treatment. Our results showed that Tween (R) 80 coated Compritol (R) and Precirol (R) LN can effectively inhibit the growth of C6 glioma cells in vitro and suggest that edelfosine-loaded LN represent an attractive option for the enhancement of antitumor activity on brain tumors in vivo. (C) 2011 Elsevier B.V. All rights reserved.

【 授权许可】

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