药物包载对两亲嵌段共聚物胶束形态的影响

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

以聚(ε-己内酯-b-L-丙交酯)/聚乙二醇单甲醚(P(CL-b-LLA)-b-mPEG)和聚(ε-己内酯-b-D,L-丙交酯)/聚乙二醇单甲醚(P(CL-b-DLLA)-b-mPEG)两种两亲嵌段共聚物为载体,选择了物理状态完全不同、而疏水性相近的吲哚美辛和维生素E为模型药物,研究了药物包载对高分子胶束形态的影响.发现两种药物在高分子胶束内部的增溶均会导致胶束形态发生显著改变,变化行为与胶束内核的结晶性和药物疏水性有关.另外,还研究了两种嵌段共聚物的载药性能,发现非结晶性疏水内核共聚物的药物包载率明显大于可结晶疏水内核的共聚物.

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（ε-caprolactone-b-L- lactide） （ P （ CL-b-LLA ）） or amorphous poly（ε-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.