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An In Vitro Human Small Intestine Tissue Model for Drug Permeation Studies

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 2R44GM108164-02
Agency Tracking Number: R44GM108164
Amount: $1,329,781.00
Phase: Phase II
Program: SBIR
Solicitation Topic Code: 300
Solicitation Number: PA14-071
Solicitation Year: 2014
Award Year: 2016
Award Start Date (Proposal Award Date): 2016-02-01
Award End Date (Contract End Date): 2019-01-31
Small Business Information
Ashland, MA 01721-1716
United States
DUNS: 147365936
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (508) 881-6771
Business Contact
Phone: (508) 881-6771
Research Institution

DESCRIPTIONprovided by applicantApproximatelyof currently marketed drugs are orally administered formulations whose clinical efficacy critically depends on the absorption from the small intestineSMIHowevercurrently available in vitro intestinal models rely predominantly on cancer cell lines that do not recapitulate theD microenvironment of the small intestineLikewiseanimal models often fail short in predicting in vivo human outcomes of candidate drugsDuring Phase Iwe successfully developed a promising small intestine drug permeation model based on an in vitroorganotypic tissue comprised of human SMI cellsCharacterization of the in vitro SMI tissues showed good correspondence to native human tissue in terms of histologytransepithelial electrical resistanceand structural featuresThe utility of the SMI model for drug permeation studies was demonstratedIn vitro SMI permeability data strongly correlated with in vivo human absorption datarwhereas data from the widely used Cacocell line model was less predictiverPermeability data also demonstrated that efflux transporters were functional in the SMI in vitro tissue and inhibition studies showed that the SMI tissue will likely be useful to study drug drug interactionsAn economic analysis of the in vitro model showed significant advantages versus comparable rodent bioavailability studiesThe ultimate goal of this project is produce a validatedbiologically relevant organotypic SMI model that predicts intestinal drug absorption bioavailability of orally administered drugsThe human in vivo like characteristics of the SMI model and its capacity to measure drug absorptionmetabolismand drug drug interactions make it a superior tool to existing in vitro and ex vivo methodsIn the proposed applicationwe will finalize a drug permeation and metabolism prediction modelReproducibility of the model will be determined and transferability of the in vitro assay methods to other laboratories will be demonstratedSuccessful completion of these Phasegoals will result in an extremely useful model for early preclinical drug screeningThe human primary cell based SMI tissue model will improve pharmacokinetic analysis of new drug formulationsaccelerate drug developmentand reduce the everincreasing development cost of drugs

* Information listed above is at the time of submission. *

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