Microfluidic Manufacture of Lipid-Based Nanomedicines

Abstract

Nanoparticulate technologies have revolutionized drug delivery allowing for passive and active targeting, altered biodistribution, controlled drug release (temporospatial or triggered), enhanced stability, improved solubilization capacity, and a reduction in dose and adverse effects. However, their manufacture remains immature, and challenges exist on an industrial scale due to high batch-to-batch variability hindering their clinical translation. Lipid-based nanomedicines remain the most widely approved nanomedicines, and their current manufacturing methods remain discontinuous and face several problems such as high batch-to-batch variability affecting the critical quality attributes (CQAs) of the product, laborious multistep processes, need for an expert workforce, and not being easily amenable to industrial scale-up involving typically a complex process control. Several techniques have emerged in recent years for nanomedicine manufacture, but a paradigm shift occurred when microfluidic strategies able to mix fluids in channels with dimensions of tens of micrometers and small volumes of liquid reagents in a highly controlled manner to form nanoparticles with tunable and reproducible structure were employed. In this review, we summarize the recent advancements in the manufacturing of lipid-based nanomedicines using microfluidics with particular emphasis on the parameters that govern the control of CQAs of final nanomedicines. The impact of microfluidic environments on formation dynamics of nanomaterials, and the application of microdevices as platforms for nanomaterial screening are also discussed.