Castile J D, Taylor K M
Department of Pharmaceutics, School of Pharmacy, University of London, Brunswick Square, London, UK.
Int J Pharm. 1999 Oct 15;188(1):87-95. doi: 10.1016/s0378-5173(99)00207-0.
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 phosphatidylcholine 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.
本文描述了一种使用冻融挤压方法生产脂质体的方案的开发。激光衍射粒度分析表明，当双层中包含胆固醇时，冻融后的鸡蛋磷脂酰胆碱多层囊泡（eggPC MLVs）的中值直径会增加。在-196℃的液氮中冷冻3分钟，然后在50℃解冻3分钟的冻融循环导致eggPC/胆固醇制剂的粒径异常大。当脂质体反复冻融时，在五个冻融循环后达到最大尺寸。脂质体在氯化钠溶液中的分散促进了冻融后的尺寸增加，这表明囊泡已经聚集或融合。泊洛沙姆P338和P407抑制了分散在1.0 M NaCl中的eggPC MLVs在冻融过程中观察到的尺寸增加，这可能是通过空间位阻防止聚集和融合实现的。
