Novel biodegradable polylactide/poly(ethylene glycol) micelles prepared by direct dissolution method for controlled delivery of anticancer drugs.
OBJECTIVE
The aim of this study is to develop novel polylactide/poly(ethylene glycol) (PLA/PEG) micelles as carrier of hydrophobic drug (paclitaxel) by direct dissolution method without using any organic solvents. The in vitro and in vivo release properties were studied in comparison with micelles prepared by dialysis.


METHODS
Drug encapsulation efficiency (EE) and loading content (LC) of the micelles were evaluated by high-performance liquid chromatography. Micelle diameters and structures were determined by dynamic light scattering and transmission electron microscopy. In vitro release was performed in phosphate-buffered saline (pH 7.4) at 37 degrees C, and in vivo experiments were realized in lung cancer-bearing mice.


RESULTS
Similar EE and LC values were obtained for micelles by direct dissolution method and those by dialysis. L- and D-PLA/PEG mixed micelles present higher drug encapsulation ability than separate micelles due to stereocomplexation. Micelle diameters are enlarged by drug-loading. Faster drug release was obtained for micelles by direct dissolution than those by dialysis. Compared with current clinical formulation and micelles by dialysis, paclitaxel-loaded micelles by direct dissolution showed the highest antitumor ability.


CONCLUSIONS
The L- and D-PLA/PEG mixed micelles by direct dissolution method present many advantages such as easy formulation and absence of toxic organic solvents, which shows great potential as carrier of hydrophobic drugs.
Yang
Liu
L
Department of Materials Science, Fudan University, Shanghai, 200433, China.
Wu
Xiaohan
X
Liu
Feng
F
Duan
Yourong
Y
Li
Suming
S
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001672:Biocompatible Materials / Q000138:chemical synthesis*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008823:Micelles; D011091:Polyesters / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000493:pharmacokinetics; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D000972:Antineoplastic Agents, Phytogenic; D001672:Biocompatible Materials; D008823:Micelles; D011091:Polyesters; D011092:Polyethylene Glycols; C033616:poly(lactide)