Dexamethasone nano-aggregates composed of PEG-PLA-PEG triblock copolymers for anti-proliferation of smooth muscle cells

Abstract

Dexamethasone nano-aggregate was prepared for the treatment of intimal hyperplasia caused by abnormal proliferation of smooth muscle cells. Triblock copolymers composed of poly(ethylene glycol) [PEG] and poly(D,L-lactic acid) [PLA] were synthesized with different chain lengths of PEG. Triblock copolymers in organic phase were mixed with dexamethasone and dexamethasone nano-aggregates was prepared by dispersing the organic phase into water. The average diameter of the nano-aggregates ranged from 200 to 300 nm. Dexamethasone was released out from the nano-aggregates and the release profile was dependent on PEG chain lengths. The dexamethasone nano-aggregates showed superior anti-proliferation effects on smooth muscle cells compared to dexamethasone. Flow cytometry showed that smooth muscle cells treated with dexamethasone nano-aggregates was arrested at a dormant phase in a dose-dependent manner. The dexamethasone nano-aggregates are expected to be a potent candidate for anti-proliferating smooth muscle tissues after a balloon-catheter treatment. (c) 2006 Published by Elsevier B.V.