Journal
COLLOID AND POLYMER SCIENCE
Volume 283, Issue 9, Pages 954-967Publisher
SPRINGER
DOI: 10.1007/s00396-004-1243-8
Keywords
poly(methoxy-polyethyleneglycol polycaprolactone); micelle surface properties; hydrocamptothecin; pharmacokenitics; biodistribution
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The amphiphilic copolymer of poly(methoxy-polyethyleneglycol polycaprolactone) (MePEG-PCL) was synthesized. Micelles loading hydroxycamptothecin (HCPT) as a model drug were prepared by solid-dispersion and dialysis-hydration method. The MePEG-PCL micelles were further characterized in terms of critical association concentrations (CAC), PEG surface density, fixed aqueous layer thickness, in vitro drug release and in vivo pharmacokinetics and biodistribution. The results showed that longer polycaprolactone (PCL) chain length would lead to the reduction of CAC value, stabilized HCPT, increasing drug-loading coefficient, sparser PEG surface density and slower drug release patterns. On the other hand, longer PEG chain length would give rise to less negative zeta potential and larger fixed aqueous layer thickness, as well as sparser PEG surface density and quicker drug release. MePEG-PCL micelles with PEG molecular weight of 2,000, 5,000, 10,000 could extend the AUC of HCPT in blood compartment by 9.13, 13.82, 21.25 times and increase the AUC of I-125-HCPT in the tumor of S-180 mice by 7.94, 11.32, 26.08-fold, respectively. It was suggested that the PEG and PCL chain length may play a very important role in the micelle's in vitro properties and in vivo behavior.
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