阳离子脂质组成对寡核苷酸/乳液复合物性质的影响:物理化学及释放研究。
Effect of cationic lipid composition on properties of oligonucleotide/emulsion complexes: Physico-chemical and release studies.
作者信息
Martini Erico, Fattal Elias, de Oliveira Mônica Cristina, Teixeira Helder
机构信息
Programa de Pós-graduação em Ciências Farmacêuticas da Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga 2752, 90610-000 Porto Alegre, RS, Brazil.
出版信息
Int J Pharm. 2008 Mar 20;352(1-2):280-6. doi: 10.1016/j.ijpharm.2007.10.032. Epub 2007 Oct 30.
This paper describes the influence of cationic lipid composition on physico-chemical properties of complexes formed between oligonucleotides (ON) and cationic emulsions. Formulations containing medium chain triglycerides, egg lecithin, increasing amounts of either oleylamine (OA) or 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), and water were prepared by a spontaneous emulsification procedure. ON adsorption on emulsions was evidenced by the inversion of the zeta-potential, the increase in droplet size, and the morphology of the oil droplet examined through transmission electron microscopy. Adsorption isotherms showed a higher amount of ON adsorbed on emulsions containing DOTAP when compared to emulsions containing OA. In a final step, the role of the main parameters, which may in fact influence the ON release rate from emulsions, was investigated. ON were progressively released from emulsions with an increase in dilution ratio and remained quite similar for both OA and DOTAP emulsions over time. Conversely, the effect of the cationic lipid composition was observed upon increasing the charge ratio of complexes. ON release at a same charge ratio was lower from emulsions containing DOTAP (bearing dioleyl chains) than from those containing OA (bearing monoleyl chain).
本文描述了阳离子脂质组成对寡核苷酸(ON)与阳离子乳液形成的复合物物理化学性质的影响。通过自发乳化程序制备了含有中链甘油三酯、蛋黄卵磷脂、逐渐增加的油胺(OA)或1,2 - 二油酰基 - 3 - 三甲基铵丙烷(DOTAP)以及水的制剂。通过zeta电位反转、液滴尺寸增加以及透射电子显微镜检查的油滴形态证明了ON在乳液上的吸附。吸附等温线表明,与含有OA的乳液相比,含有DOTAP的乳液吸附的ON量更高。在最后一步中,研究了可能实际上影响ON从乳液中释放速率的主要参数的作用。随着稀释比的增加,ON从乳液中逐渐释放,并且随着时间的推移,OA和DOTAP乳液的释放情况相当相似。相反,在增加复合物的电荷比时观察到了阳离子脂质组成的影响。在相同电荷比下,含有DOTAP(带有二油酰链)的乳液中ON的释放低于含有OA(带有单油酰链)的乳液。