Permeability Of Hydrophilic :: essays research papers

Permeability of HydrophilicSupervisors Vladan Milovic Professor Per Artursson digestInvestigations of the integrity and institutionalise characteristics of 2/4/A1 cellshave been done in this report. The cell line was isolated from rat fetalintestinal epithelial cells and transfected with thermolabile SV40 large Tantigen.These cells proliferated at 33 C, but eliminated the antigen and ceasedproliferating at a non-permissive temperature (39C). At 39C 2/4/A1 cellsstarted to contrast but simultaneously the cells also underwent massivecell death.When cultured at 37C these cells formed confluent and tight mono forges thatseemed to have paracellular delight characteristics similar to that of thehuman intestine. Transmission electron microscopy confirmed the development ofmultilayers at 33C, monolayers at 37C and defects in the cell layer due toapoptosis at 39C.Different immunostainings of ZO-1, E-cadherin and vinculin confirmed constitutionof tight and adherence junctions. Transepithel ial resistance reached a plateauof 25-35 Ohm.cm2, which was similar to the atomic intestine. In transport studies2/4/A1 cell line monolayers selectively restricted the permeation of deliquescentpermeability markers proportional to molecular gouget and discriminated moreaccurately between the molecules of intermediate molecular weight comp ared toCaco-2 cells.These results indicated that 2/4/A1 cells could be used as a model forhydrophilic drug absorption.INTRODUCTIONThe small intestine plays a crucial theatrical role in the absorption of drugs andnutrients. Exogenous substances cross a series of barriers during the wreakof intestinal absorption (1) the aqueous boundary/mucus layer, (2) a singlelayer of epithelial cells, and (3) the lamina propria, which contains the bloodand lymph vessels that then transport the absorbed drugs to early(a) parts of thebody (Artursson 1991).The cell monolayer is comprised of two parallel barriers the cell tissue layer andthe tight junctions. M ost drugs are absorbed by a dormant diffusion crosswise thecell membrane by the transcellular route, or across the tight junctions betweenthe cells - the paracellular route. Drug transport evict also be carrier mediated,when the drug utilizes transporters located in the cellular membrane.Transcytosis is another multifariousness of active transport, in which macromolecules can betransported across the intestinal epithelial cell in endocytosed vesicles.The hydrophilic and charged drugs are absorbed afterward passing through theparacellular route, the water-filled channels between the cells (Artursson1991). Rates and extent of the paracellular transport are, therefore, highlyinfluenced by the structure and size of the tight junctions as considerably as by thesize of the molecules. Only small and hydrophilic drugs can pass between thecells rapidly and completely permeation of larger molecules can be limitedproportionally to their size and lipophilicity (Hillgren et al. 1995).Simple assay methods are needed for drug absorption studies.