# A new high-throughput gastrointestinal tract explant platform for drug formulation discovery and metabolic disease modulation

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2021 · $1,068,674

## Abstract

Project Summary/Abstract
Our long-term goal is the development of systems providing controlled drug delivery of a broad set of
therapeutics including those that are limited to parenteral routes. In this proposal, we build on our prior work to
focus on the gastrointestinal (GI) barrier and specifically propose a platform enabling the high-throughput GI
transport evaluation of novel formulations rapidly. Developing therapies which are compatible with oral
administration, requires significant formulation and in vitro and in vivo evaluation for maximal oral bioavailability
in humans. Current in vitro models of GI absorption are limited by their throughput and approximation of the
physiologic state. Consequently, we propose: 1) the development of systems enabling prolonged culturing of
intact mammalian GI tissue coupled to 2) high-throughput robotics to transform formulation development and
study of the GI tract. These investigations are supported by strong preliminary data demonstrating: 1) culture
conditions which maintain the presence of a broad set of cellular markers and drug transporters ex vivo in
porcine GI tissue, 2) fabrication of prototype systems enabling high-throughput interrogation, 3) demonstration
of predictive capacity of drug absorption for a large panel of drugs, 4) demonstration of near order of
magnitude enhancement of uptake of a model molecule following a large-scale excipient screen. Currently,
promising therapeutics which are poorly absorbed through the oral route can manifest in drug development
delays on the order of years and many times no formulation solution is identified. The proposed work will target
a critical unmet clinical need by providing tools to rapidly identify formulations that enable: maximal drug
solubility and absorption and minimal local toxicity. Moreover, the proposed system will enable interrogation
and study of the GI tract entero-endocrine system enabling the discovery of new therapies for metabolic
disorders. Through this proposal we will develop a novel set of formulations and novel material-drug
combinations enabling the oral delivery of drugs previously restricted to parenteral routes. Moreover, we will
develop novel modulators of the enteroendocrine system providing novel solutions to the metabolic disease
epidemic. In sum, this proposal aims to provide a platform akin to an ‘intestine-on-a-chip’ with the capacity to
transform formulation science and the study of the GI tract with the potential to transform treatments for
metabolic disease and other diseases of the GI tract.

## Key facts

- **NIH application ID:** 10152644
- **Project number:** 5R01EB000244-42
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** ROBERT Samuel LANGER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,068,674
- **Award type:** 5
- **Project period:** 1979-07-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10152644

## Citation

> US National Institutes of Health, RePORTER application 10152644, A new high-throughput gastrointestinal tract explant platform for drug formulation discovery and metabolic disease modulation (5R01EB000244-42). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10152644. Licensed CC0.

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