Factors affecting the size distribution of liposomes produced by freeze-thaw extrusion

被引:92
作者
Castile, JD [1 ]
Taylor, KMG [1 ]
机构
[1] Univ London, Sch Pharm, Dept Pharmaceut, London WC1N 1AX, England
基金
英国生物技术与生命科学研究理事会;
关键词
extrusion; freeze-thaw; liposome; particle size; poloxamer;
D O I
10.1016/S0378-5173(99)00207-0
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
This paper describes the development of a protocol for the production of liposomes using a freeze-thaw extrusion methodology. Laser diffraction particle size analysis showed that the median diameter of freeze-thawed egg phosphalidylcholine multilamellar vesicles (eggPC MLVs) was increased when cholesterol was included in the bilayers. Using a freeze-thaw cycle of 3 min freezing in liquid nitrogen at - 196 degrees C followed by 3 min thawing at 50 degrees C resulted in an anomalously large particle size for eggPC/cholesterol formulations. When liposomes were repeatedly freeze-thawed a maximum size was achieved after five freeze-thaw cycles. Dispersion of liposomes in sodium chloride solutions promoted size increases following freeze-thawing, suggesting that vesicles had aggregated or fused. Poloxamers P338 and P407 inhibited the size increases observed during freeze-thawing for eggPC MLVs dispersed in 1.0 M NaCl, probably through steric prevention of aggregation and fusion. (C) 1999 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:87 / 95
页数:9
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