THE IMPACT OF PERMEABILITY ENHANCERS ON ASSESSMENT FOR MONOLAYER OF COLON ADENOCARCINOMA CELL LINE (CACO-2) USED IN IN VITRO PERMEABILITY ASSAY

Abstract

The leading goal in new drug discovery is to have orally bioavailable drug. Poor permeability is one of the reasons for the poor bioavailability of several New Chemical Entities (NCEs). Permeability assessment using in vitro Caco-2 cell monolayer model is considered to be excellent model for screening of NCEs. Permeability enhancers can increase the permeability of compounds by paracellular or transcellular route. There are limitations to use the permeability enhancers due to concentration dependent toxic effect on cell monolayer, several times wrong interpretation can be made due to disrupted cell monolayer integrity. This study was performed on Caco-2 cell monolayer to identify optimal levels of commonly used permeability enhancers which does not cause any damage to the cell monolayer. The assessment involved pre and post TEER measurement and leak test using Lucifer yellow (LY) rejection assay. Total 16 permeability enhancers were tested and optimum levels were as per parenthesis: peanut oil (10%), Cremphore EL, Miglyol 812, Oleic acid, Propylene glycol (1%), Capmul MCM C8 EP, glycerol, Labrasol, MC8-2, PEG 400, Polysorbate 80, Sporiol TPGS, Transcutol (0.1% ), Capmul , Solutol (0.01% ) and for PPS (0 .0001%). It was important to determine the optimal levels of each permeability enhancer to avoid any false positive results. Keywords: Permeability enhancers, Caco-2 cell line, TEER, % LY rejection, Tight Junctions