Effect of PEO-PPO-PEO triblock copolymers on structure and stability of phosphatidylcholine liposomes
Effect of PEO-PPO-PEO triblock copolymers on structure and stability of phosphatidylcholine liposomes
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DOI：
10.1021/la990288
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发表时间：
1999-09-14
期刊：
影响因子：
3.9
通讯作者：
Edwards, K
中科院分区：
文献类型：
--
作者：
Johnsson, M;Silvander, M;Edwards, K
研究了五种聚氧乙烯(poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene)-PPO-PEO)、Pluronic、共聚物与不同组成的磷脂酰胆碱脂质体之间的相互作用。通过低温电子显微镜(c-TEM)的结构研究发现，低含量的Pluronics(类似于2mol%)的包合会引起脂质体的形态发生显著的变化。含有大的聚氧乙烯(PEO)嵌段的Pluronics，如F127、F108和F87，可诱导双层盘的形成，而具有相对较短的PEO嵌段的Pluronics，如P105和P85，则倾向于促进脂质体尺寸的减小。在脂质体制剂中加入胆固醇会减少共聚物在脂质双层中的掺入，从而减少，在某些情况下甚至取消了在没有胆固醇的情况下观察到的形态变化。同时考察了共聚物对脂质体渗透性的影响。所有研究的共聚物都能增加羧基荧光素从预制脂质体中的渗漏。在含胆固醇脂质体的情况下也是如此，尽管通过c-TEM观察不到脂质体结构的变化。通过CMC测量，发现诱导泄漏的大小与相应的Pluronic的疏水性有很好的相关性。通过提高温度或降低共聚物在溶液中的溶解度，发现共聚物对脂质体渗漏的影响显著增加。
The interactions of five poly(oxyethylene)-poly(oxypropylene)-poly(oxyethylene) (PEO-PPO-PEO), Pluronic, copolymers and phosphatidylcholine liposomes of varying composition have been studied. Structural studies were performed by means of cryo-transmission electron microscopy (c-TEM) and reveal that inclusion of low amounts (similar to 2 mol %) of Pluronics gives rise to significant morphological changes of the liposome preparations. Pluronics with large poly(oxyethylene) (PEO) blocks, such as F127, F108, and F87, induce the formation of bilayer disks, whereas those with comparably short PEO blocks, P105 and P85, tend to to promote a reduction in the liposome size. Inclusion of cholesterol in the liposomal preparations reduces the incorporation of copolymers in the lipid bilayer and thus reduces, and in some cases even abolishes, the morphological changes observed in the absence of cholesterol. The effect of the copolymers on liposome permeability was also investigated. All investigated copolymers were found to increase the leakage of carboxyfluorescein from preformed liposomes. This was true also in the case of cholesterol-containing Liposomes despite the fact that no change in the liposome structure could be observed by means of c-TEM. The magnitude of the induced leakage was found to correlate well with the hydrophobicity, as measured by the cmc, of the respective Pluronic. By raising the temperature or decreasing the solvency of the copolymer in the solution, the effect of the copolymer on liposome leakage was found to increase significantly.