Pham Hoang L, Ross Benjamin P, McGeary Ross P, Shaw P Nicholas, Davies Nigel M
The University of Queensland, School of Pharmacy, Brisbane, QLD, Australia.
Int J Pharm. 2009 Jul 6;376(1-2):123-33. doi: 10.1016/j.ijpharm.2009.04.011. Epub 2009 Apr 16.
The aim of the study was to prepare cationic ISCOMs using cationic derivatives of the saponin Quil A. The polyamines ethylenediamine, spermidine and spermine were conjugated with the glucuronic acid moiety of Quil A. The aqueous solubility of the derivatives increased with decreasing pH, and the pK(a) values were between 6 and 7. The CMCs of the ionised derivatives were around 0.5-1.0 mg/mL. Using the method of hydration of freeze-dried monophase systems, the interaction of each of the Quil A derivatives with phosphatidylcholine and cholesterol, at a mass ratio of 4:4:2 and a pH of 3 and 7.4, was investigated. A few ISCOM-like structures were present in the systems prepared at pH 7.4, hence the ternary system of Quil A spermine derivative, phosphatidylcholine and cholesterol was further investigated at pH 7.4 using a variety of mass ratios. A relatively high number of cationic ISCOM-like structures were observed at the mass ratio of 6:2:2. These ISCOM-like structures were less homogeneous and more irregular in shape than ISCOMs prepared from unmodified Quil A. Colloidal particles with positive zeta potential were produced and may find application in the delivery of nucleic acids or anionic proteins.
本研究的目的是使用皂苷基尔A的阳离子衍生物制备阳离子免疫刺激复合物（ISCOM）。将多胺乙二胺、亚精胺和精胺与基尔A的葡萄糖醛酸部分共轭。衍生物的水溶性随pH值降低而增加，其pK(a)值在6至7之间。离子化衍生物的临界胶束浓度（CMC）约为0.5 - 1.0 mg/mL。采用冻干单相体系水合的方法，研究了在质量比为4:4:2且pH值为3和7.4的条件下，每种基尔A衍生物与磷脂酰胆碱和胆固醇的相互作用。在pH值为7.4时制备的体系中存在一些类似ISCOM的结构，因此在pH值为7.4时，使用多种质量比进一步研究了基尔A精胺衍生物、磷脂酰胆碱和胆固醇的三元体系。在质量比为6:2:2时观察到相对大量类似阳离子ISCOM的结构。这些类似ISCOM的结构比由未修饰的基尔A制备的ISCOM更不均匀，形状更不规则。产生了具有正ζ电位的胶体颗粒，其可能在核酸或阴离子蛋白的递送中得到应用。
