Here we report a microfluidic system that enables rapid and efficient remote loading of amphipathic drugs into nanoscale liposomes, combining liposome synthesis and remote drug loading in a continuous integrated process. Unlike established bulk methods for remote drug loading, in which each process step is performed in a series of discrete manual operations using large fluid volumes, the microfluidic system incorporates liposome formation, buffer exchange, and liposome/drug mixing and incubation in a continuous-flow process. The platform (Fig. 1) takes advantage of an established microfluidic hydrodynamic flow focusing method for the formation of functionalized, nearly monodisperse liposomes.1620 The liposome synthesis technology is extended here with the addition of a counterflow microdialysis element, enabling steep transmembrane ion gradients to be formed immediately prior to remote drug loading. The system further implements a drug loading and incubation zone that includes micromixer structures to enhance interactions between liposomes and amphipathic compounds during the remote loading process. The resulting device decreases the processing time for liposome preparation and remote drug loading from a multi-day process to less than 3 minutes, with resulting D/L values up to 5 times greater than typical liposomal therapeutics prepared by conventional bulk scale processes.
Citation: Lab on A Chip
Pub Type: Journals
active loading, liposomes, microfluidics, drug delivery