Lipid microfluidic biomimetic models for drug screening: a comprehensive review

Abstract

Developing new drugs is a complex, time-consuming, and expensive process, essential to identify potential pharmacokinetic issues in the early stages to avoid investment in nonpromising candidates. Nearly half of all drug targets and key drug-metabolizing enzymes are found in intracellular environments, compartmentalized by semipermeable barriers, the cell membranes. Inspired by their lipidic bilayer structure, lipid-based biomimetic platforms are being developed to understand the biochemical and biophysical processes at the cellular membrane level. Considering the pharmaceutical industry's demands for efficient in vitro high throughput screening tools, microfluidic technology emerges as a promising solution to address challenges in lipid biomimetic models for screening applications. This involves the transformation of commonly used lipid-based biomimetic models, like supported lipid bilayers and lipid vesicles, to miniaturized approachs and their evolution into a new generation of bilayer models. These include pore-suspended and free-standing lipid bilayers, black lipid membranes, and droplet interface bilayers. This review provides an overview of both generations of lipid biomimetic models used in drug-membrane screening applications. Moreover, it delves into the intricacies of their production through microfluidic approaches and examines their screening applications in drug-membrane interaction. The review concludes with a critical analysis of potential future directions in this rapidly evolving field.