Pharmacokinetics and biodistribution of polymeric micelles of paclitaxel with Pluronic P123.
OBJECTIVE
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 centigrade degree. In the pharmacokinetic assessment, t(1/2beta) 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.


CONCLUSIONS
Polymeric micelles using Pluronic P123 can effectively solubilize PTX, prolong blood circulation time and modify the biodistribution of PTX.
Han
Li-Mei
LM
Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 200032, China.
Guo
Jie
J
Zhang
Li-Jun
LJ
Wang
Qing-Song
QS
Fang
Xiao-Ling
XL
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005260:Female; D051379:Mice; D008823:Micelles; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010316:Particle Size; D011060:Poloxalene / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014018:Tissue Distribution
D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008823:Micelles; C464484:pluronic block copolymer P123; D011060:Poloxalene; D017239:Paclitaxel