title: An acoustically-driven biochip - impact of flow on the cell-association of targeted drug carriers.
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 (2.9 +/- 1 microm) were conjugated with wheat germ agglutinin (WGA-MP, cytoadhesive protein) or bovine serum albumin (BSA-MP, non-specific protein) and their binding to epithelial cell monolayers was investigated under stationary and flow conditions. While mean numbers of 1500 +/- 307 mm(-2) WGA-MP and 94 +/- 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 +/- 241 mm(-2) and 104 +/- 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.
authors: Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, A-1090, Vienna, Austria.
authors: Christian
authors: C
authors: Fillafer
authors: Gerda
authors: G
authors: Ratzinger
authors: Jürgen
authors: J
authors: Neumann
authors: Zeno
authors: Z
authors: Guttenberg
authors: Silke
authors: S
authors: Dissauer
authors: Irene K
authors: IK
authors: Lichtscheidl
authors: Michael
authors: M
authors: Wirth
authors: Franz
authors: F
authors: Gabor
authors: Matthias F
authors: MF
authors: Schneider
mesh_terms: D000162:Acoustics; D002448:Cell Adhesion; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D010316:Particle Size; D046888:Tissue Array Analysis / Q000295:instrumentation / Q000379:methods*; D014407:Tumor Cells, Cultured
chemical_list: D004337:Drug Carriers