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Pharmacokinetics and biodistribution of polymeric micelles of paclitaxel with Pluronic P123

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Abstract:

Abstract

Aim: To investigate the preparation, in vitro release, in vivo pharmacokinetics and tissue distribution of a novel polymeric micellar formulation of paclitaxel (PTX) with Pluronic P123. Methods: The polymeric micelles of paclitaxel with Pluronic P123 were prepared by a solid dispersion method. The characteristics of micelles including particle size distribution, morphology and in vitro release of PTX from micelles were carried out. PTX-loaded micellar solutions were administered through the tail vein to healthy Sprague-Dawley rats and Kunming strain mice to assess the pharmacokinetics and tissue distribution of PTX, respectively. Taxol, the commercially available intravenous formulation of PTX, was also administered as control. Results: By using a dynamic light scattering sizer and a transmission electron microscopy, it was shown that the PTX-loaded micelles had a mean size of approximately 25 nm with narrow size distribution and a spherical shape. PTX was continuously released from Pluronic P123 micelles in release medium containing 1 mol/L sodium salicylate for 24 h at 37°C. In the pharmacokinetic assessment, t1/2 and AUC of micelle formulation were 2.3 and 2.9-fold higher than that of Taxol injection. And the PTX-loaded micelles increased the uptake of PTX in the plasma, ovary and uterus, lung, and kidney, but decreased uptake in the liver and brain in the biodistribution study. Conclusion: Polymeric micelles using Pluronic P123 can effectively solubilize PTX, prolong blood circulation time and modify the biodistribution of PTX.

Keywords: Pluronic P123; biodistribution; micelle; paclitaxel; pharmacokinetics

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1745-7254.2006.00340.x

Affiliations: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 200032, China

Publication date: June 1, 2006

bsc/aphs/2006/00000027/00000006/art00016
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