1. Eur J Pharm Biopharm. 2009 Oct;73(2):230-8. Epub 2009 Jul 3.

Novel self-assembling PEG-p-(CL-co-TMC) polymeric micelles as safe and effective 
delivery system for Paclitaxel.

Danhier F, Magotteaux N, Ucakar B, Lecouturier N, Brewster M, Préat V.

Université Catholique de Louvain, Unité de Pharmacie Galénique, Brussels B-1200, 
Belgium.

Paclitaxel (PTX) is an effective anti-cancer drug currently used to treat a wide 
variety of cancers. Unfortunately, nonaqueous vehicle containing Cremophor EL is 
associated with serious clinical side effects. This work aimed to evaluate the
ability of polymeric micelles to (i) solubilize PTX without Cremophor EL and to
be used as a (ii) safe and (iii) effective delivery system for PTX. Hence, we
developed novel self-assembling
poly(ethyleneglycol)(750)-block-poly(epsilon-caprolactone-co-trimethylenecarbonat
e) (PEG-p-(CL-co-TMC)) polymeric micelles which form micelles spontaneously in
aqueous solution. The solubility of PTX increased up to three orders of
magnitude. The PTX-loaded micelles showed a slow release of PTX with no burst
effect. The HeLa cells viability assessed by the MTT test was lower for
PTX-loaded micelles than for Taxol (IC(50) 10.6 vs. 17.6 microg/ml). When
solubilized in micelles, PTX induced apoptosis comparable with Taxol. The maximum
tolerated doses (MTD) of PTX-loaded micelles and Taxol in mice were 80 mg/kg and 
13.5mg/kg, respectively, after intraperitoneal administration; and 45 mg/kg and
13.5mg/kg, respectively, after intravenous administration. Similar anti-tumor
efficacy of PTX-loaded micelles and Taxol was observed at the dose of 13.5mg/kg
on TLT-tumor-bearing mice, while the body weight loss was only observed in Taxol 
group. However, as higher dose was tolerated (80 mg/kg - IP), a higher growth
delay was induced with PTX-loaded micelles. These results demonstrated that
PTX-loaded self-assembling micelles present a similar anti-tumor efficacy as
Taxol, but significantly reduced the toxicity allowing the increase in the dose
for better therapeutic response.

PMID: 19577643 [PubMed - in process]