# Treating Second-Degree Burn Wound Infections with a Quorum Sensing Inhibitor

> **NIH NIH R43** · IONIC PHARMACEUTICALS · 2024 · $300,000

## Abstract

ABSTRACT
We propose a treatment to overcome infection by methicillin-resistant Staphylococcus aureus (MRSA) via a new
mechanism of action: “quorum sensing inhibition”. MRSA is the most prevalent opportunistic pathogen implicated
in burn wounds and once a sufficient number of bacteria colonize a wound (i.e., a “quorum”), they communicate
via the Accessory Gene Regulator (Agr) pathway to upregulate virulence factor production and invasion via cell-
cell signaling. Halting this communication (i.e., quorum sensing inhibition) is a powerful means of hamstringing
MRSA virulence, and thereby augmenting host immune response, that does not rely on traditional antibiotics. w-
Hydroxyemodin is a new natural product (fungal secondary metabolite) that we have recently demonstrated
provides robust quorum sensing inhibition when administered topically. To deliver w-hydroxyemodin topically,
we propose to use a novel, sprayable hydrogel-based burn wound dressing: the HydrAid Wound Dressing. This
dressing is sprayed-on easily and quickly, gelling in situ to form a soft, elastic and mechanically robust hydrogel
dressing significantly faster than commercial hydrogel sheets (or other Advanced Dressings) can be applied
(especially over complex surfaces, e.g., hands, feet, elbows). To change the dressing, a dissolution solution is
applied that dissolves the gel within minutes thereby alleviating or averting altogether the mechanical peeling
and unintentional debridement that cause intractable pain and trauma for patients and caregivers alike. Thus,
the w-hydroxyemodin-loaded HydrAid dressing overcomes the dual challenges of bacterial infection and patient
pain common to the majority of 2nd degree burn wounds. Importantly, this combination product is intended as an
adjuvant to current antibiotic regimens. While future clinical success may warrant investigation as a monother-
apy, until such time, due to the polymicrobial nature of wound infections and the fact that not all pathogens utilize
the Agr pathway, combination with traditional antibiotics will be a clinical necessity. As part of an ongoing Phase
II SBIR (R44 GM125412) we have already established large-scale production of HydrAid dressing material com-
ponents, demonstrated utility (of the unloaded version) in vivo and are manufacturing prototypes and evaluating
pain metrics in a large-animal burn model. For the present application, in which w-hydroxyemodin is loaded in
the HydrAid dressing, we have demonstrated the ability to load and release therapeutically relevant levels of w-
hydroxyemodin and to combat MRSA infections in vivo in mice by augmenting the immune system and reducing
MRSA virulence. This project addresses three key inflection points on the critical path for further development of
this technology, including: Aim 1: Optimize the w-hydroxyemodin-loaded HydrAid wound dressing formulation to
provide sustained release of therapeutic concentrations of w-hydroxyemodin for three days. Aim 2: Determine
th...

## Key facts

- **NIH application ID:** 10916626
- **Project number:** 1R43AI183989-01
- **Recipient organization:** IONIC PHARMACEUTICALS
- **Principal Investigator:** Aaron Henry Colby
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $300,000
- **Award type:** 1
- **Project period:** 2024-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10916626

## Citation

> US National Institutes of Health, RePORTER application 10916626, Treating Second-Degree Burn Wound Infections with a Quorum Sensing Inhibitor (1R43AI183989-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10916626. Licensed CC0.

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