期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 436, 期 1-2, 页码 258-264出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2012.06.030
关键词
Stabilized micelles; Paclitaxel; Pluronic; Gastrointestinal transit; Oral absorption
资金
- Ministry of Science and Innovation [SAF2008-02538]
- Grant PFIS (Instituto de Salud Carlos III)
- Foundation Caja Navarra: Tu eliges, tu decides (Nanotecnologia y Medicamentos) in Spain [10828]
- National Science Fund of Bulgaria (National Centre for New Materials UNION) [DCVP-02/2]
Paclitaxel is an antineoplastic drug used against a variety of tumors, but its low aqueous solubility and active removal caused by P-glycoprotein in the intestinal cells hinder its oral administration. In our study, new type of stabilized Pluronic micelles were developed and evaluated as carriers for paclitaxel delivery via oral or intravenous route. The pre-stabilized micelles were loaded with paclitaxel by simple solvent/evaporation technique achieving high encapsulation efficiency of approximately 70%. Gastrointestinal transit of the developed micelles was evaluated by oral administration of rhodamine-labeled micelles in rats. Our results showed prolonged gastrointestinal residence of the marker encapsulated into micelles, compared to a solution containing free marker. Further, the oral administration of micelles in mice showed high area under curve of micellar paclitaxel (similar to the area of i.v. Taxol (R)), longer mean residence time (9-times longer than i.v. Taxol (R)) and high distribution volume (2-fold higher than i.v. Taxol (R)) indicating an efficient oral absorption of paclitaxel delivered by micelles. Intravenous administration of micelles also showed a significant improvement of pharmacokinetic parameters of micellar paclitaxel vs. Taxol (R), in particular higher area under curve (1.2-fold), 5-times longer mean residence time and lower clearance, indicating longer systemic circulation of the micelles. (c) 2012 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据