Permeability Of Hydrophilic :: essays research papers

Permeability of hydrophilicSupervisors Vladan Milovic Professor Per ArturssonSUMMARYInvestigations of the integrity and ecstasy characteristics of 2/4/A1 booths commence been done in this report. The cell line was isolated from rat foetalintestinal 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 differentiate but simultaneously the cells also underwent massivecell death.When cultured at 37C these cells formed confluent and ladened monolayers thatseemed to have paracellular transport characteristics similar to that of thehuman intestine. Transmission electron microscopy confirm the development ofmultilayers at 33C, monolayers at 37C and defects in the cell layer due toapoptosis at 39C. opposite immunostainings of ZO-1, E-cadherin and vinculin confirmed formationof airless and adherence junctions. Transep ithelial resistance reached a plateauof 25-35 Ohm.cm2, which was similar to the microscopic intestine. In transport studies2/4/A1 cell line monolayers selectively restricted the interpenetration of hydrophilicpermeability markers relative to molecular(a) weight and discriminated moreaccurately between the molecules of intermediate molecular weight comp bed 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 role in the absorption of drugs andnutrients. Exogenous substances cross a series of barriers during the processof intestinal absorption (1) the aqueous boundary/ mucous secretion 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 other parts of thebody (Artursson 1991).The cell monolayer is comprised of two analog barriers the cell membrane andthe tight junctions . Most drugs are absorbed by a passive diffusion across thecell membrane by the transcellular route, or across the tight junctions betweenthe cells - the paracellular route. Drug transport basis also be carrier mediated,when the drug utilizes transporters located in the cellular membrane.Transcytosis is another kind of active transport, in which macromolecules can betransported across the intestinal epithelial cell in endocytosed vesicles.The hydrophilic and charged drugs are absorbed after passing through theparacellular route, the water-filled channels between the cells (Artursson1991). rank and extent of the paracellular transport are, therefore, highlyinfluenced by the structure and size of the tight junctions as well 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). unbiased assay methods are neede d for drug absorption studies.