Controlled liposome formation and solute encapsulation with continuous-flow microfluidic hydrodynamic focusing

Abstract

Liposomes enable the compartmentalization of compounds making them interesting as drug delivery systems. A drug delivery system (DDS) is a transport vehicle for a drug for in vivo drug administration. Drugs can be encapsulated, bound, or otherwise tethered to the carrier which can vary in size from tens of nanometers to a few micrometers. Liposomal DDSs have shown their capability to deliver drugs in a new fashion, allowing exclusive sales of encapsulated drugs to be extended beyond the initial compound's patent expiration date. However, existing methods to form liposomes and encapsulate drugs are based on bulk mixing techniques with limited process control and the produced liposomes frequently require post-processing steps. In this dissertation, a new method is demonstrated to control liposome formation and compound encapsulation that pushes beyond existing benchmarks in liposome size homogeneity and adjustable encapsulation. The technology utilizes microfluidics for future pharmacy-on-a-chip applications. The microfluidic system allows for precise control of mixing via molecular diffusion with reproducible and controlled physicochemical conditions compared to traditional bulk-phase preparation techniques (i.e. test tubes and beakers). The laminar flow and facile fluidic control in microchannels enables reproducible self-assembly of lipids into liposomes in a sheathed flow-field. Confining a water-soluble compound to be encapsulated to the immediate vicinity where liposome formation is expected to occur reduces sample consumption without affecting liposome loading. The ability to alter the concentration and control the amount of encapsulated compounds within liposomes in a continuous-flow mode is another interesting feature towards tailored liposomal drug delivery. The liposome formation strategy demonstrated in this dissertation offers potential for point-of-care drug encapsulation, eliminating shelf-life limitations inherent to current liposome preparation techniques.