Liposome Formation Using a Coaxial Turbulent Jet in Co-Flow.

Abstract

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 >465nm. 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.