Costa Antonio P, Xu Xiaoming, Khan Mansoor A, Burgess Diane J
Department of Pharmaceutical Sciences, University of Connecticut, 69 N Eagleville Rd U3092, Storrs, Connecticut, 06269, USA.
FDA/CDER/DPQR, 10903 New Hampshire Ave, WO64 RM1076, Silver Spring, Maryland, 20993, USA.
Pharm Res. 2016 Feb;33(2):404-16. doi: 10.1007/s11095-015-1798-8. Epub 2015 Oct 1.
Liposomes are robust drug delivery systems that have been developed into FDA-approved drug products for several pharmaceutical indications. Direct control in producing liposomes of a particular particle size and particle size distribution is extremely important since liposome size may impact cellular uptake and biodistribution.
A device consisting of an injection-port was fabricated to form a coaxial turbulent jet in co-flow that produces liposomes via the ethanol injection method. By altering the injection-port dimensions and flow rates, a fluid flow profile (i.e., flow velocity ratio vs. Reynolds number) was plotted and associated with the polydispersity index of liposomes.
Certain flow conditions produced unilamellar, monodispersed liposomes and the mean particle size was controllable from 25 up to >465 nm. The mean liposome size is highly dependent on the Reynolds number of the mixed ethanol/aqueous phase and independent of the flow velocity ratio.
The significance of this work is that the Reynolds number is predictive of the liposome particle size, independent of the injection-port dimensions. In addition, a new model describing liposome formation is outlined. The significance of the model is that it relates fluid dynamic properties and lipid-molecule physical properties to the final liposome size.
脂质体是强大的药物递送系统,已被开发成用于多种药物适应症的、获美国食品药品监督管理局(FDA)批准的药品。由于脂质体大小可能影响细胞摄取和生物分布,因此直接控制特定粒径和粒径分布的脂质体的生产极为重要。
制造了一种由注射端口组成的装置,以在并流中形成同轴湍流射流,通过乙醇注射法生产脂质体。通过改变注射端口尺寸和流速,绘制了流体流动曲线(即流速比与雷诺数),并将其与脂质体的多分散指数相关联。
某些流动条件产生了单层、单分散的脂质体,平均粒径可在25至>465nm范围内控制。脂质体平均大小高度依赖于乙醇/水混合相的雷诺数,而与流速比无关。
这项工作的意义在于雷诺数可预测脂质体粒径,与注射端口尺寸无关。此外,概述了一种描述脂质体形成的新模型。该模型的意义在于它将流体动力学性质和脂质分子物理性质与最终脂质体大小联系起来。