# Topical and systemic interventions for mustard-induced skin injury

> **NIH NIH U54** · NORTHWESTERN UNIVERSITY · 2024 · $558,547

## Abstract

SUMMARY
Sulfur mustard (SM) is a reactive bifunctional alkylating agent that reacts with a variety of small molecules and
macromolecules such as DNA. SM was used as a chemical warfare agent during World War I and many times
thereafter. SM and nitrogen mustard (NM) cause severe epithelial and deep tissue injury characterized by acute
inflammation, induration, swelling, and blistering upon contact. The influx of immune cells first by neutrophils
followed by monocytes and macrophages provide defense to the damaged epithelium; however, with time,
persistent inflammation results in an immune storm that incurs additional tissue damage resulting in a long
recovery process. Treatment of SM injuries is complicated due to the complexity of the mustard-induced injury
combined with variables of exposure concentration and time to therapy. Thus, novel therapies to prevent the
deleterious effects of SM exposure is a major unmet need. Our goal is to develop countermeasures using
topical and systemic interventions. Specifically we will focus on switching off key cellular events upstream
in the injury cascade to limit the immune storm and induction of tissue matrix factors. To achieve this
goal, we will undertake a comprehensive nanoparticle-based approach to 1) block monocytes and macrophages
from entering injured skin and 2) stabilize SM injured skin to block further release of chemo-attractants for
immune cells. We have shown that a high dose systemic administration of vitamin D3 suppresses innate immune
cell activity and ameliorates damage to the skin and circulating blood cells following SM and NM exposure.
Therefore, combinations of novel nanoparticle-based materials with vitamin D3 may yield positive treatment
results. The novel particles that we will test are (i) i.v. administration of poly (lactic-co-glycolic acid) immune
modifying microparticles (PLGA-IMPs). These particles have anti-inflammatory properties because they block
monocytes and neutrophils from leaving the vessels and entering into sites of tissue injury; (ii) topical application
of synthetic, functional high-density lipoprotein nanoparticles (HDL NPs) inherently enhance re-epithelialization
following wounding and can act as anti-inflammatory agents; and (iii) topical application of a synthetic mimic of
melanin using dopamine formed into spherical polydopamine nanoparticles (PDA NPs). These particles reduce
NM-induced inflammation and edema. Our strategy is use systemic infusion of PLGA-IMP to block monocyte
and macrophages to mitigate skin and systemic manifestations from NM and SM exposure. We will use HDL
NP to target skin and immune cells NF-kB activity, and we will use PDA NPs to topically block acute inflammation.
We will also investigate the efficacy of these particles in combination with vitamin D3. Ultimately, these
investigations will yield unique treatments for SM-induced injury that will have anti-inflammatory, pro-resolving,
capacity with minimal side effects. These novel drugs a...

## Key facts

- **NIH application ID:** 10907613
- **Project number:** 5U54AR079795-04
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Kurt Lu
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $558,547
- **Award type:** 5
- **Project period:** 2021-09-17 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10907613

## Citation

> US National Institutes of Health, RePORTER application 10907613, Topical and systemic interventions for mustard-induced skin injury (5U54AR079795-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10907613. Licensed CC0.

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