Arunothayanun P, Turton J A, Uchegbu I F, Florence A T
Centre for Drug Delivery Research, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, UK.
J Pharm Sci. 1999 Jan;88(1):34-8. doi: 10.1021/js980286u.
Niosomes are vesicles formed by the self-assembly of nonionic surfactants in aqueous dispersions. They can entrap drugs and have been used experimentally as sustained drug delivery systems. Apart from conventional spherical niosomes, various types of vesicle ultrastructures can be formed by varying the composition of the vesicle membrane. Hexadecyl diglycerol ether (C16G2), cholesterol, and poly-24-oxyethylene cholesteryl ether (Solulan C24) in the ratio 91:0:9 gave polyhedral niosomes, whereas spherical and tubular niosomes are produced at a composition ratio of 49:49:2. The mean size of both polyhedral and spherical/tubular niosomes were within the range of 6 to 9 microm. Both types of vesicle were visualized by cryo-scanning electron microscopy. The properties of the two forms of niosomes were studied using luteinizing hormone releasing hormone (LHRH) as a model peptide. Analysis by high-performance liquid chromatography demonstrated high entrapment of LHRH acetate in polyhedral niosomes when prepared by remote loading methods using pH or (NH4)2SO4 gradients; in contrast, only low entrapment was achieved by passive loading methods (direct hydration at pH 7.4 or pH 3.0, dehydration-rehydration, and reversed-phase evaporation). In vitro studies demonstrated that both polyhedral and spherical/tubular niosomes were more stable in 5% rat skeletal muscle homogenate than in rat plasma. Also, polyhedral niosomes released more radiolabeled LHRH ([125I]LHRH) than spherical/tubular niosomes in both muscle homogenate and plasma. In clearance experiments in the rat, following intramuscular injection, both polyhedral and spherical/tubular niosomes gradually released [125I]LHRH into the blood, but some radioactivity remained at the injection site for 25 and 49 h, respectively. In contrast, [125I]LHRH in phosphate buffered saline was completely cleared from the injection site at 2 h. The release of drug is sustained by both niosome formulations, but spherical/tubular niosomes possess more stable membranes than polyhedral niosomes due to the presence of cholesterol.
非离子表面活性剂在水分散体系中自组装形成的囊泡即为非离子表面活性剂泡囊。它们能够包封药物，并且已被用作实验性的缓释给药系统。除了常规的球形非离子表面活性剂泡囊外，通过改变泡囊膜的组成还可以形成各种类型的泡囊超微结构。十六烷基二甘油醚（C16G2）、胆固醇和聚-24-氧乙烯胆固醇醚（Solulan C24）按91:0:9的比例可得到多面体非离子表面活性剂泡囊，而在组成比例为49:49:2时可产生球形和管状非离子表面活性剂泡囊。多面体和球形/管状非离子表面活性剂泡囊的平均大小均在6至9微米范围内。两种类型的泡囊均通过冷冻扫描电子显微镜观察到。以促黄体生成素释放激素（LHRH）作为模型肽，对两种形式的非离子表面活性剂泡囊的性质进行了研究。高效液相色谱分析表明，当采用pH梯度或硫酸铵梯度的远程加载方法制备时，多面体非离子表面活性剂泡囊中醋酸盐形式的LHRH包封率很高；相比之下，被动加载方法（在pH 7.4或pH 3.0下直接水化、脱水再水化以及反相蒸发）只能实现较低的包封率。体外研究表明，多面体和球形/管状非离子表面活性剂泡囊在5%大鼠骨骼肌匀浆中比在大鼠血浆中更稳定。此外，在肌肉匀浆和血浆中，多面体非离子表面活性剂泡囊释放的放射性标记LHRH（[125I]LHRH）比球形/管状非离子表面活性剂泡囊更多。在大鼠的清除实验中，肌肉注射后，多面体和球形/管状非离子表面活性剂泡囊均逐渐将[125I]LHRH释放到血液中，但分别有一些放射性在注射部位残留25小时和49小时。相比之下，磷酸盐缓冲盐水中的[125I]LHRH在2小时时从注射部位完全清除。两种非离子表面活性剂泡囊制剂均能实现药物的持续释放，但由于胆固醇的存在，球形/管状非离子表面活性剂泡囊的膜比多面体非离子表面活性剂泡囊更稳定。
