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

用于药物渗透研究的体外人体小肠组织模型

基本信息

  • 批准号:
    9049151
  • 负责人:
  • 金额:
    $ 64.88万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2014
  • 资助国家:
    美国
  • 起止时间:
    2014-07-01 至 2018-07-31
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): Approximately 60% of currently marketed drugs are orally administered formulations whose clinical efficacy critically depends on the absorption from the small intestine (SMI). However, currently available in vitro intestinal models rely predominantly on cancer cell lines that do not recapitulate the 3D microenvironment of the small intestine. Likewise, animal models often fail short in predicting in vivo human outcomes of candidate drugs. During Phase I, we successfully developed a promising small intestine drug permeation model based on an in vitro, organotypic tissue comprised of human SMI cells. Characterization of the in vitro SMI tissues showed good correspondence to native human tissue in terms of histology, transepithelial electrical resistance, and structural features. The utility of the SMI model for drug permeation studies was demonstrated. In vitro SMI permeability data strongly correlated with in vivo human absorption data (r2 = 0.87 - 0.95) whereas data from the widely-used Caco-2 cell line model was less predictive (r2 = 0.81). Permeability 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 interactions. An economic analysis of the in vitro model showed significant advantages versus comparable rodent bioavailability studies. The ultimate goal of this project is produce a validated, biologically relevant organotypic SMI model that predicts intestinal drug absorption/bioavailability of orally administered drugs. The human in vivo-like characteristics of the SMI model and its capacity to measure drug absorption, metabolism, and drug-drug interactions make it a superior tool to existing in vitro and ex-vivo methods. In the proposed application, we will finalize a drug permeation and metabolism prediction model. Reproducibility of the model will be determined and transferability of the in vitro assay methods to other laboratories will be demonstrated. Successful completion of these Phase 2 goals will result in an extremely useful model for early preclinical drug screening. The human primary cell based SMI tissue model will improve pharmacokinetic analysis of new drug formulations, accelerate drug development, and reduce the ever- increasing development cost of drugs.


项目成果

期刊论文数量(0)
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会议论文数量(0)
专利数量(0)

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Seyoum Ayehunie其他文献

Seyoum Ayehunie的其他文献

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{{ truncateString('Seyoum Ayehunie', 18)}}的其他基金

Organotypic Culture Models (OCM) developed from experimental animals for Chemical Toxicity Screening.
器官培养模型 (OCM) 由用于化学毒性筛选的实验动物开发而成。
  • 批准号:
    10079739
  • 财政年份:
    2020
  • 资助金额:
    $ 64.88万
  • 项目类别:
An In Vitro Human Small Intestine Tissue Model for Drug Permeation Studies
用于药物渗透研究的体外人体小肠组织模型
  • 批准号:
    9210635
  • 财政年份:
    2014
  • 资助金额:
    $ 64.88万
  • 项目类别:
An In Vitro Human Small Intestine Tissue Model for Drug Permeation Studies
用于药物渗透研究的体外人体小肠组织模型
  • 批准号:
    8714269
  • 财政年份:
    2014
  • 资助金额:
    $ 64.88万
  • 项目类别:
Use of a CB2 Ligand to prevent HIV-1 Infection and Transmission
使用 CB2 配体预防 HIV-1 感染和传播
  • 批准号:
    8602723
  • 财政年份:
    2013
  • 资助金额:
    $ 64.88万
  • 项目类别:
Use of a CB2 Ligand to prevent HIV-1 Infection and Transmission
使用 CB2 配体预防 HIV-1 感染和传播
  • 批准号:
    8681359
  • 财政年份:
    2013
  • 资助金额:
    $ 64.88万
  • 项目类别:
In Vitro Human Tissue Model for Intravaginal Drug Delivery
用于阴道内药物输送的体外人体组织模型
  • 批准号:
    7910090
  • 财政年份:
    2010
  • 资助金额:
    $ 64.88万
  • 项目类别:
Validation of a Human In Vitro Vaginal Irritation Test
人体体外阴道刺激试验的验证
  • 批准号:
    7220081
  • 财政年份:
    2007
  • 资助金额:
    $ 64.88万
  • 项目类别:
Validation of Human Vaginal Tissue Assay for Endocrine Disruptors
人体阴道组织内分泌干扰物检测的验证
  • 批准号:
    8207929
  • 财政年份:
    2007
  • 资助金额:
    $ 64.88万
  • 项目类别:
Validation of a Human In Vitro Vaginal Irritation Test
人体体外阴道刺激试验的验证
  • 批准号:
    7937022
  • 财政年份:
    2007
  • 资助金额:
    $ 64.88万
  • 项目类别:
Validation of Organotypic Vaginal Tissue Based Assay for Endocrine Disruptors
基于器官型阴道组织的内分泌干扰物测定的验证
  • 批准号:
    7270190
  • 财政年份:
    2007
  • 资助金额:
    $ 64.88万
  • 项目类别:

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