# Polymer Epithelial Lining for the Oral Delivery of Macromolecules

> **NIH NIH R44** · SYNTIS BIO INC · 2024 · $349,160

## Abstract

PROJECT SUMMARY
Macromolecule drugs, specifically peptides, are an attractive therapeutic class given they are more potent and
target specific than small molecules yet demonstrate superior tissue permeation and manufacturability compared
to large proteins. As such, they are one of the most clinically and commercially viable therapeutic modalities for
treating chronic conditions such as metabolic disease, ageing, infectious disease, and inflammatory disorders.
Peptides however are also highly biodegradable, poorly absorbed in the GI tract, and rapidly cleared from the
body which has necessitated administration via repeated injections. These constant injections create significant
burden for patients, especially those managing chronic disease, and thus result in poor adherence. While
molecular structural modifications, enteric coatings and permeation enhancing excipients (PEs) have marked
major advances in oral delivery technologies, the critical challenge of sufficient GI absorption has not been solved.
A key hurdle has been the dynamic intestinal environment, where variable contents and rapid gastric emptying
result in insufficient co-localization of the target therapeutic agent and PE excipients. Consequently, the addition
of large amounts of PEs to current oral macromolecule formulations results in only a minor improvement in
absorption. Syntis’ Gastrointestinal Synthetic Epithelial Lining (GSEL) technology is synthetic tissue platform that
enterically delivers a mucoadhesive polydopamine (PDA) lining to the small intestine. When GSEL is co-
formulated with therapeutic agents, these compounds are incorporated into the PDA lining to create an evenly
distributed drug depot that lasts between 18-24 hours, significantly increasing GI residence time and thus
systemic absorption of the target drug compound. In pigs, GSEL has demonstrated the ability to increase the
half-life of anti-parasitic drug praziquantel tenfold, and total absorption (AUC) fourfold. In this SBIR Fast-Track
proposal. we propose to build on the previous oral delivery work achieved with praziquantel to enable peptide
macromolecule compounds. To demonstrate the broad applicability of the GSEL platform, we propose to identify
GSEL-compatible formulations of model peptide drugs and permeation enhancers, optimize composition for co-
localization and depot formation in the small intestine, and create tablets of lead formulations for oral delivery.
At the successful conclusion of the work described herein, the next steps will be to finalize raw materials sourcing
for GMP manufacturing, initiate GLP toxicity studies with a CRO, and finalize a clinical plan for a first-in-human
single ascending dose study.

## Key facts

- **NIH application ID:** 10917514
- **Project number:** 1R44DK138869-01A1
- **Recipient organization:** SYNTIS BIO INC
- **Principal Investigator:** Vasu V Sethuraman
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $349,160
- **Award type:** 1
- **Project period:** 2024-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10917514

## Citation

> US National Institutes of Health, RePORTER application 10917514, Polymer Epithelial Lining for the Oral Delivery of Macromolecules (1R44DK138869-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10917514. Licensed CC0.

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