  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.
