# Impact of lipids and food on oral compound absorption: mechanistic studies and modeling

> **NIH NIH R01** · NORTHEASTERN UNIVERSITY · 2021 · $392,500

## Abstract

The overall goal of this project is to enable mechanistic understanding and quantitative prediction of the
influence of ingested lipids and food on orally delivered compound absorption. Lipids and food can enhance
oral absorption of some compounds several hundred percent; however, they can also cause several-fold
decreases in absorption, or have no effect. These effects are not currently amenable to quantitative prediction,
yet hold tremendous significance with respect to drug delivery, nutrition, and food-related diseases. While
previous studies have probed specific aspects of lipid and food function in the gastrointestinal (GI) tract, it is
proposed that an integrated, systems based approach considering multiple parallel, dynamic processes
(compound dissolution, lipid digestion, partitioning into colloidal phases, absorption) will enable quantitative
understanding and prediction. An experimental and theoretical framework has been developed by the PI's lab
and used successfully to predict the impact of lipids (long chain triglycerides) on drug absorption and
pharmacokinetics (PK). In this project, we will build from these initial efforts to enable understanding and
prediction of the impact of complex food composition and structure. In the first aim, the impact of complex food
structure and composition on kinetics of digestion and co-delivered compound dissolution/partitioning into
colloids will be studied. While it is recognized that food composition and structure are highly variable and
complex, the proposed approach is to systematically test the impact of increasing complexity on physical and
chemical properties of a controlled dynamic biorelevant in vitro system, coupled with analysis of the inherently
variable in vivo digestion system. Compounds studied will represent broad ranges of relevant physicochemical
properties. In the second aim, the impact of lipids and food on mucosal transport processes will be explored in
detail. Specifically, the stability of mixed bile micelles containing lipid digestion products in the intestinal mucus
barrier will be studied using electron paramagnetic resonance (EPR), and the potential impact of lipid
transcellular transport on co-delivered compound transport, including tendency for lymphatic transport, will be
studied. A novel primary human intestinal tube model will be employed to enable visualization of the mucosal
interface in these studies. Finally, in the third aim, the ability of the model to predict PK in vivo, including
human food effect data, will be validated. The research team embodies the multidisciplinary expertise
necessary to transform fundamental knowledge of lipid digestion to quantitative prediction: a chemical engineer
with experimental and modeling expertise in lipid-based oral drug delivery, mucosal transport, and engineered
intestinal systems; a chemist with expertise in EPR analysis of complex microenvironments, a bioengineer with
advanced biomaterial and organ-on-chip expertise, and...

## Key facts

- **NIH application ID:** 10201616
- **Project number:** 5R01GM098117-08
- **Recipient organization:** NORTHEASTERN UNIVERSITY
- **Principal Investigator:** Rebecca L Carrier
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $392,500
- **Award type:** 5
- **Project period:** 2012-07-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201616

## Citation

> US National Institutes of Health, RePORTER application 10201616, Impact of lipids and food on oral compound absorption: mechanistic studies and modeling (5R01GM098117-08). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10201616. Licensed CC0.

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