# Localized delivery of glycosaminoclycan ethers for the treatment of radiation-induced proctitis

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $342,013

## Abstract

ABSTRACT
Radiation-induced proctitis (RIP) is often considered a chronic inflammatory disease involving the
rectum. Pathologic studies have shown patient symptoms are correlated with inflammatory
lesions along the epithelium lining the rectum. This grant application proposes to combine novel
sulfated anionic polysaccharides, semisynthetic glycosaminoglycan ethers (SAGEs) with silk-
elastinlike protein polymer (SELP) matrices to deliver therapeutically relevant doses in the rectum
via a precisely engineered in situ gelling enema. SELPs exist as aqueous solutions at room
temperature, and form a solid hydrogel matrix at body temperature, enabling them to prevent
rapid clearance of the SAGE and enhance its localization in the lumen of the rectum and lower
bowel. We hypothesize that localized delivery of SAGE can protect the rectum from damage
caused by radiotherapy and improve efficacy by ameliorating RIP. To test this hypothesis three
specific aims are proposed: 1) To synthesize and characterize SELPs with appropriate rheological
properties and release profiles for rectal delivery of SAGE; 2) To investigate the biodistribution
and efficacy of SAGE delivered from SELP hydrogels in a murine model of radiation-induced
proctitis; 3) To elucidate mast cells as a key effector cell type in radiation-induced proctitis and
assess SAGE in SELP hydrogels’ ability to attenuate mast cell mediated proctitis. This proposal
is translational in nature and innovative in the new indication for use of recombinant SELPs to
deliver our patented SAGE compounds with potent anti-inflammatory and anti-pain properties.
The project is significant in that it will reduce the adverse effects of RIP in the affected patient
populations. This work will establish the early-stage preclinical validation for these two systems
and provide detailed knowledge about the inflammation and pain attenuation properties of the
SAGE-SELP compounds.

## Key facts

- **NIH application ID:** 9816617
- **Project number:** 5R01CA227225-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Hamid Ghandehari
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $342,013
- **Award type:** 5
- **Project period:** 2018-12-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9816617

## Citation

> US National Institutes of Health, RePORTER application 9816617, Localized delivery of glycosaminoclycan ethers for the treatment of radiation-induced proctitis (5R01CA227225-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9816617. Licensed CC0.

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