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由二嵌段共聚物制成的囊泡的制备、稳定性及体外性能

Preparation, stability, and in vitro performance of vesicles made with diblock copolymers.

作者信息

Lee J C, Bermudez H, Discher B M, Sheehan M A, Won Y Y, Bates F S, Discher D E

机构信息

School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA.

出版信息

Biotechnol Bioeng. 2001 Apr 20;73(2):135-45. doi: 10.1002/bit.1045.

Abstract

Vesicles made completely from diblock copolymers-polymersomes-can be stably prepared by a wide range of techniques common to liposomes. Processes such as film rehydration, sonication, and extrusion can generate many-micron giants as well as monodisperse, approximately 100 nm vesicles of PEO-PEE (polyethyleneoxide-polyethylethylene) or PEO-PBD (polyethyleneoxide-polybutadiene). These thick-walled vesicles of polymer can encapsulate macromolecules just as liposomes can but, unlike many pure liposome systems, these polymersomes exhibit no in-surface thermal transitions and a subpopulation even survive autoclaving. Suspension in blood plasma has no immediate ill-effect on vesicle stability, and neither adhesion nor stimulation of phagocytes are apparent when giant polymersomes are held in direct, protracted contact. Proliferating cells, in addition, are unaffected when cultured for an extended time with an excess of polymersomes. The effects are consistent with the steric stabilization that PEG-lipid can impart to liposomes, but the present single-component polymersomes are far more stable mechanically and are not limited by PEG-driven micellization. The results potentiate a broad new class of technologically useful, polymer-based vesicles.

摘要

完全由二嵌段共聚物制成的囊泡——聚合物囊泡——可以通过多种与脂质体相同的常见技术稳定制备。诸如薄膜水化、超声处理和挤压等过程可以产生许多微米大小的巨型囊泡以及单分散的、约100纳米的聚环氧乙烷-聚乙撑乙烯(PEO-PEE)或聚环氧乙烷-聚丁二烯(PEO-PBD)囊泡。这些聚合物制成的厚壁囊泡可以像脂质体一样包裹大分子,但与许多纯脂质体系统不同的是,这些聚合物囊泡没有表面热转变,甚至有一部分能经受高压灭菌。悬浮于血浆中对囊泡稳定性没有立即的不良影响,当巨型聚合物囊泡直接、长时间接触时,也未观察到黏附或对吞噬细胞的刺激现象。此外,当与过量的聚合物囊泡长时间共培养时,增殖细胞不受影响。这些效应与聚乙二醇脂质赋予脂质体的空间稳定作用一致,但目前的单组分聚合物囊泡在机械性能上要稳定得多,且不受聚乙二醇驱动的胶束化限制。这些结果为一类新的、具有广泛技术用途的基于聚合物的囊泡奠定了基础。

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