title: A microdevice for parallelized pulmonary permeability studies.
abstract: We describe a compartmentalized microdevice specifically designed to perform permeability studies across a model of lung barrier. Epithelial cell barriers were reproduced by culturing Calu-3 cells at the air-liquid interface (AIC) in 1 mm² microwells made from a perforated glass slide with an embedded porous membrane. We created a single basolateral reservoir for all microwells which eliminated the need to renew the growth medium during the culture growth phase. To perform drug permeability studies on confluent cell layers, the cell culture slide was aligned and joined to a collection platform consisting in 35 μL collection reservoirs connected at the top and bottom with microchannels. The integrity and functionality of the cell barriers were demonstrated by measurement of trans-epithelial electrical resistance (TEER), confocal imaging and permeability assays of ¹⁴C-sucrose. Micro-cell barriers were able to form confluent layers in 1 week, demonstrating a similar bioelectrical evolution as the Transwell systems used as controls. Tight junctions were observed throughout the cell-cell interfaces, and the low permeability coefficients of ¹⁴C-sucrose confirmed their functional presence, creating a primary barrier to the diffusion of solutes. This microdevice could facilitate the monitoring of biomolecule transport and the screening of formulations promoting their passage across the pulmonary barrier, in order to select candidates for pulmonary administration to patients.
authors: Faculté de Pharmacie, Université Paris-Sud, 92290, Châtenay-Malabry, France.
authors: Ludivine
authors: L
authors: Bol
authors: Jean-Christophe
authors: JC
authors: Galas
authors: Hervé
authors: H
authors: Hillaireau
authors: Isabelle
authors: I
authors: Le Potier
authors: Valérie
authors: V
authors: Nicolas
authors: Anne-Marie
authors: AM
authors: Haghiri-Gosnet
authors: Elias
authors: E
authors: Fattal
authors: Myriam
authors: M
authors: Taverna
mesh_terms: D015824:Blood-Air Barrier / Q000166:cytology / Q000378:metabolism*; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods; D002460:Cell Line; D017097:Electric Impedance; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods; D010539:Permeability; D013395:Sucrose / Q000493:pharmacokinetics*; D013549:Sweetening Agents / Q000493:pharmacokinetics*
chemical_list: D013549:Sweetening Agents; D013395:Sucrose