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Conception d’un microsystème pour l’évaluation du passage de biomolécules à travers la barrière pulmonaire

Abstract : The pulmonary route is of increasing interest for the systemic administration of therapeutic proteins and peptides, still largely administered parenterally. A microdevice was designed to facilitate and accelerate the in vitro screening studies of various active biomolecules and to select the most suitable formulations for penetration through the lung epithelium, in order to select the best candidates for an administration via the lungs. Organized in two distinct configurations, this microdevice allows as a first step the culture of tight polarized bronchial epithelial barriers (Calu-3 cells) in 7 days in 1 mm² microwells, without the need for medium renewal or the use of an external apparatus. A simple manufacturing technique was developed and glass culture platforms containing 12 parallel microwells can be obtained in a standardized manner. The ability of molecules to cross the pulmonary barrier is then performed in the second configuration of the microdevice, which is dedicated to the permeability measurement of the tight epithelial Calu-3 barriers cultured in microwells. Among the different candidates studied (nanoparticules and biomolecules), the pulmonary barrier permeability regarding PLGA nanoparticules coated with chitosan and regarding insulin has been successfully demonstrated. Finally, capillary electrophoresis with laser induced-fluorescence (CE-LIF), a technique compatible with the low volumes handled in this microdevice, has been exploited for insulin detection and quantification after its transport across the miniaturized pulmonary barriers. To this end, insulin was either FITC-labeled or complexed with a fluorescent antibody or aptamer. Currently, only the derivatization method can be used for a quantification purpose, but the use of an aptamer to indirectly quantitate insulin has shown encouraging results.
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Submitted on : Monday, September 8, 2014 - 4:22:08 PM
Last modification on : Wednesday, October 14, 2020 - 4:00:17 AM
Long-term archiving on: : Thursday, December 11, 2014 - 3:20:47 PM


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  • HAL Id : tel-01061867, version 1



Ludivine Bol. Conception d’un microsystème pour l’évaluation du passage de biomolécules à travers la barrière pulmonaire. Autre. Université Paris Sud - Paris XI, 2014. Français. ⟨NNT : 2014PA112118⟩. ⟨tel-01061867⟩



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