Pham H L, Shaw P N, Davies N M
School of Pharmacy, The University of Queensland, St. Lucia, Brisbane 4072, QLD, Australia.
Int J Pharm. 2006 Mar 9;310(1-2):196-202. doi: 10.1016/j.ijpharm.2005.11.011. Epub 2006 Jan 18.
This study investigated the application of the solvent dispersion technique, specifically ether injection, which has been successfully used in the preparation of liposomes, as a new, continuous and potentially scaleable method for the preparation of ISCOMs. Phosphatidylcholine (PC) and cholesterol (Chol) were dissolved in ether, which was injected into an aqueous solution, maintained at 55 degrees C, containing Quil A. The influences of the following variables on ISCOM formation were investigated: ratio of PC:Quil A:Chol used, pumping rate, total lipid mass and concentration of buffer salts and Quil A in the aqueous phase. All samples were characterized by negative stain transmission electron microscopy, photon correlation spectroscopy and sucrose ultracentrifugation gradient. It was demonstrated that ISCOMs could be produced by this method but the homogeneity of the preparation was influenced by the conditions used. Homogeneous ISCOM preparations were consistently produced only when the weight ratio of PC:Quil A:Chol was 5:3:2 with a total lipid mass of 20 mg, the Quil A dissolved in a 0.01 M phosphate buffer at a concentration of 6 mg in 4 ml, and the ether solution injected into the warmed buffer solution at a rate of 0.2 ml/min. Changing any of these variables resulted in more heterogeneous preparations in which ISCOMs typically co-existed with other colloidal structures such as worm-like and helical micelles, liposomes, lamellae and lipidic particles.
本研究考察了溶剂分散技术，特别是乙醚注入法的应用，该方法已成功用于脂质体的制备，作为一种新型、连续且具有潜在放大规模能力的iscom制备方法。将磷脂酰胆碱（PC）和胆固醇（Chol）溶解于乙醚中，然后将其注入保持在55℃的含有Quil A的水溶液中。研究了以下变量对iscom形成的影响：所用PC:Quil A:Chol的比例、泵送速率、总脂质质量以及水相中缓冲盐和Quil A的浓度。所有样品均通过负染透射电子显微镜、光子相关光谱和蔗糖超速离心梯度法进行表征。结果表明，该方法可以制备iscom，但制备的均匀性受所用条件的影响。只有当PC:Quil A:Chol的重量比为5:3:2、总脂质质量为20 mg、Quil A溶解于0.01 M磷酸盐缓冲液中且浓度为4 ml含6 mg、乙醚溶液以0.2 ml/min的速率注入温热的缓冲溶液中时，才能始终如一地制备出均匀的iscom制剂。改变这些变量中的任何一个都会导致制剂更加不均一，其中iscom通常与其他胶体结构如蠕虫状和螺旋状胶束、脂质体、片层和脂质颗粒共存。
