An acoustically-driven biochip - Impact of flow on the cell-association of targeted drug carriers

TL;DR

This study introduces an acoustically-driven microfluidic biochip that simulates physiological flow conditions to analyze how flow impacts the binding of targeted drug carriers to cell monolayers, aiding drug delivery system design.

Contribution

It presents a novel, biocompatible microfluidic system that accurately mimics physiological flow, allowing detailed study of drug carrier-cell interactions under dynamic conditions.

Findings

Flow inhibits binding of non-specific particles completely.

Targeted particles with WGA show strong anchoring despite flow.

The platform enables high-throughput screening of drug delivery vehicles.

Abstract

The interaction of targeted drug carriers with epithelial and endothelial barriers in vivo is largely determined by the dynamics of the body fluids. To simulate these conditions in binding assays, a fully biocompatible in vitro model was developed which can accurately mimic a wide range of physiological flow conditions on a thumbnail-format cell-chip. This acoustically-driven microfluidic system was used to study the interaction characteristics of protein-coated particles with cells. Poly(D,L-lactide-co-glycolide) (PLGA) microparticles (2.86 {\pm} 0.95 {\mu}m) were conjugated with wheat germ agglutinin (WGA-MP, cytoadhesive protein) or bovine serum albumin (BSA-MP, nonspecific protein) and their binding to epithelial cell monolayers was investigated under stationary and flow conditions. While mean numbers of 1500 {\pm} 307 mm-2 WGA-MP and 94 {\pm} 64 mm-2 BSA-MP respectively were detected to be cell-bound in the stationary setup, incubation at increasing flow velocities increasingly antagonized the attachment of both types of surface-modified particles. However, while binding of BSA-MP was totally inhibited by flow, grafting with WGA resulted in a pronounced anchoring effect. This was indicated by a mean number of 747 {\pm} 241 mm-2 and 104 {\pm} 44 mm-2 attached particles at shear rates of 0.2 s-1 and 1 s-1 respectively. Due to the compactness of the fluidic chip which favours parallelization, this setup represents a highly promising approach towards a screening platform for the performance of drug delivery vehicles under physiological flow conditions. In this regard, the flow-chip is expected to provide substantial information for the successful design and development of targeted micro- and nanoparticulate drug carrier systems.