# Development of Formulated Sevoflurane as a Novel Topical Treatment for Painful Inflammatory Conditions

> **NIH NIH R44** · VAPOGENIX, INC. · 2020 · $907,683

## Abstract

Summary/Abstract
Problem of painful inflammatory diseases: Persistent or inappropriate inflammation underlies a broad range
of painful diseases including musculoskeletal conditions, wounds and burns. Much of the inflammation and pain
associated with these diseases is due to the release of mediators from leukocytes at the site of injury. Current
treatments are often inadequate due to limited efficacy and undesirable side effects. Vapogenix (VPX) is a
clinical-stage pharmaceutical company developing a novel class of locally acting non-opioid analgesics based
on new uses, formulations and topical administration of volatile anesthetics (VAs). Current knowledge: VPX
and others have demonstrated anti-nociceptive activity of VAs when applied topically. Some VAs have also been
shown to have anti-inflammatory effects, both in vivo and in vitro. Recent publications suggest that this anti-
inflammatory effect may be partly due to the inhibition of key players in inflammation, specifically αLβ2 and αMβ2
integrins, which are known to facilitate leukocyte migration to the damaged tissue. During SBIR Phase I studies,
we showed that 5 VAs inhibited adhesion of the integrin αLβ2 to intercellular adhesion molecule-1 (ICAM-1), and
locally injected sevoflurane inhibited neutrophil migration while reducing the levels of numerous proinflammatory
cytokines in the mouse air pouch model. Based on these data, sevoflurane was chosen for formulation
development. Hypothesis: Our hypothesis is that topical formulated sevoflurane will have a dual (anti-
inflammatory and anti-nociceptive) benefit. Aims: The objective of this study is to identify a development
formulation of sevoflurane for topical application in painful inflammatory conditions. This will be accomplished by
developing and evaluating sevoflurane formulations in appropriate models (Aim 1); and by generating
pharmacology data to compare locally administered sevoflurane to known anti-inflammatory agents to support
an IND submission (Aim 2). Finally, we will prepare a briefing package for a pre-IND meeting with the FDA (Aim
3). Methods: Sevoflurane formulations will be developed and screened for penetration profile in vitro (human
skin permeation model) and anti-inflammatory activity in vivo (mouse air pouch model). The selected lead
formulation will be tested in the mono-iodoacetate-induced painful inflammation model arthritis model in rats.
Additionally, the anti-inflammatory profiles of sevoflurane in comparison to diclofenac and dexamethasone will
be examined by phenotyping leukocyte subpopulations and cytokine expression in vivo using flow cytometry and
single cell analysis. Finally, we will prepare a pre-IND briefing package in order to seek FDA feedback on our
full development program. Long term objective: VPX’s long-term goal is to develop a novel VA-based topical
product with dual anti-inflammatory and anti-nociceptive effects to treat painful inflammatory conditions with an
improved safety profile compared ...

## Key facts

- **NIH application ID:** 10077118
- **Project number:** 2R44AR074838-02
- **Recipient organization:** VAPOGENIX, INC.
- **Principal Investigator:** Heather Giles
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $907,683
- **Award type:** 2
- **Project period:** 2018-09-10 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10077118

## Citation

> US National Institutes of Health, RePORTER application 10077118, Development of Formulated Sevoflurane as a Novel Topical Treatment for Painful Inflammatory Conditions (2R44AR074838-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10077118. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*