DEVELOPMENT OF GASTROINTESTINAL TRANSPORT MODELS

DESCRIPTION (Applicant's Abstract): A major concern of any new drug is its bioavailability determined in part by its absorption and metabolism in the small intestine. Evaluation of potentially beneficial drugs in an in vitro cell culture model is essential before proceeding with more elaborate and expensive animal studies. Currently, Caco-2 cells derived from a human colon cancer are used to study drug transport in vitro. However, this model has several drawbacks. Therefore, we propose to examine an in vitro model consisting of normal human gastrointestinal cells for assessing permeability. The primary goal of this proposal is to evaluate the use of primary culture enterocytes obtained from the three regions of small intestine for use as models of gastrointestinal transport. Analyses will include establishment and optimization of conditions such as cell seeding densities, culture conditions and time of incubation required to obtain a level of confluence necessary before the cell inserts can be used for transport analysis. We will use electrical resistance and permeability coefficients as criteria for establishing the degree to tight junction integrity. The proposed transport models should reduce tissue culture time, cost and effort currently required and be very useful in determining absorption and metabolism differences of various compounds throughout the regions of the small intestine. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE