Optimisation et évaluation d’un nouveau test PAMPA amélioré pour la prédiction de l’absorption intestinale de médicaments
This essay reports the optimization and evaluation of a new version of the Parallel Artificial Membrane Permeability Assay (PAMPA), called Neo-PAMPA. This test, used for the prediction of the drugs’ intestinal absorption, involves the use of a model intestine cell membrane in which a lipid bilayer is supported on a polymeric cushion deposited on a filter.  In this project, we are interested in the development of an artificial membrane that is more representative of the human intestinal wall. We determined, based on a comparative study of the properties of 8 drug candidates and their permeability coefficients obtained, that polycarbonate filters were the best choice of solid support for the membrane. We also verified the deposition time of the polydopamine cushion that brings the fluid nature to our membrane. The results from the permeability tests showed that the polymer cushion do not clog the pores of the filter after a 4h deposition. Then, we studied the deposition of the lipid bilayer on the polydopamine-coated filter. To do this, two methods of liposome preparation as well as several liposome sizes were tested. Moreover, several phospholipid compositions were tested. According to our evaluation, liposomes prepared according to the "lipid film" method from a mixture of DOPC and cholesterol are better suited. Nevertheless, a final optimization step for the bilayer deposition is still required. Finally, the gold standard Caco-2 assay used to assess the drug permeability across a monolayer of human Colon Colorectal adenocarcinoma cells was successfully implemented for permeability data comparison.
PAMPA Polydopamine Caco-2 Drugs Caco-2 Phospholipids Polydamine PAMPA Intestinal permeability