Self-porating polymersomes of PEG-PLA and PEG-PCL: hydrolysis-triggered controlled release vesicles
Self-porating polymersomes of PEG-PLA and PEG-PCL: hydrolysis-triggered controlled release vesicles
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DOI：
10.1016/j.jconrel.2003.12.021
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发表时间：
2004-04-16
影响因子：
10.8
通讯作者：
Discher, DE
中科院分区：
文献类型：
--
作者：
Ahmed, F;Discher, DE
以可水解性聚乙二醇聚L乳酸或聚乙二醇聚己内酯两嵌段共聚物为载体制备了可控释聚合物微囊。一种常见的抗癌剂阿霉素的包封性研究表明，其载药量与脂质体相当。随着聚乙二醇比例的增加，可水解性囊泡的包封剂释放速度加快，但随着疏水性更强的链化学(即PCL)的增加，包封剂的释放速度会延迟。释放速率也随着可降解共聚物与不可降解的聚乙二醇基嵌段共聚物(聚乙二烯-聚丁二烯(PBD))共混膜中的摩尔比而线性增加。在100 nm和巨大囊泡的所有成分中，平均释放时间(从几个小时到几天)反映了一个高度量化的过程，在这个过程中，任何给定的囊泡要么完好无损并保留其包封剂，要么被穿孔并缓慢崩解。当疏水的聚乳酸或聚己内酯嵌段被水解性裂解，逐渐在膜中产生越来越多的偏孔性共聚物时，就会发生缩孔作用。这一不断演变的洗涤剂机制的动力学覆盖了两亲分子的相行为，从膜到胶束的转变允许控制释放。(C)2004爱思唯尔B.V.保留所有权利。
Controlled release polymer vesicles are prepared using hydrolysable diblock copolymers of polyethyleneglycol-poly-L-lactic acid (PEG-PLA) or polyethyleneglycol-polycaprolactone (PEG-PCL). Encapsulation studies with a common anticancer agent, doxorubicin, show loading comparable to liposomes. Rates of encapsulant release from the hydrolysable vesicles are accelerated with an increased proportion of PEG but are delayed with a more hydrophobic chain chemistry (i.e. PCL). Rates of release also rise linearly with the molar ratio of degradable copolymer blended into membranes of a non-degradable, PEG-based block copolymer (PEG-polybutadiene (PBD)). With all compositions, in both 100 nm and giant vesicles, the average release time (from hours to days) reflects a highly quantized process in which any given vesicle is either intact and retains its encapsulant, or is porated and slowly disintegrates. Poration occurs as the hydrophobic PLA or PCL block is hydrolytically scissioned, progressively generating an increasing number of pore-preferring copolymers in the membrane. Kinetics of this evolving detergent mechanism overlay the phase behavior of amphiphiles with transitions from membranes to micelles allowing controlled release. (C) 2004 Elsevier B.V. All rights reserved.