EFFECT OF DRUG INCORPORATION ON THE MORPHOLOGY OF AMPHIPHILIC BLOCK COPOLYMER MICELLES

Abstract

Two model drugs,indomethacin and vitamin E( α-tocopherol),which have different physical stae and similar hydrophobicity,were incorporated respectively into polymerc micelles in aqueous media by dialysis method. The micelles were formed from two types of biodegradable amphiphilic block copolymers based on methoxy poly(ethylene glycol)(mPEG) as a hydrophilic block and either crystalline poly(e-caprolactone-b-L- lactide) ( P ( CL-b-LLA )) or amorphous poly(e-caprolactone-b-D,L-lactide) ( P ( CL-b-DLLA )) as a hydrophobic block. The morphology and drug loading property of the polymeric micelles were characterized by transmission electron microscopy ( TEM ),laser light scattering ( LLS ),ultraviolet ( UV ) spectroscopy measureemnts. It was found that incorporating drugs into the micelles resulted in significant changes of the micellar morphologies. The different behaviors of the morphological change depended mainly on the crystalline property of the core-forming blocks. The morphology of micelles formed with P( CL-b-LLA)-b-mPEG changed from short rod-like cylinders to wormike ones; whereas those formed with P( CL-b-DLLA)-b-mPEG changed from spheres to cylinders. In addition,the transformation of the micellar morphologies upon the drug entrapment was influenced by the hydrophobicity of the drugs more significantly than by the physical state of the drugs, while the drug loading amount was affected by the comatibility between carriers and drugs. Much more liquid- like drugs were entrapped in the amphiphilic copolymers with non-crystalline core.