(LR-014) Gas Marble Technology for Chronic Wounds: A Novel Atomic Drug-delivery System Backed by Computational Discovery

Rayna Shaik, Undergraduate Student; Nabhan Fakrudin, BS; Shriya Singh, Undergraduate Student; Yeju Lee, BS; Waldo Barrientos, BS; Jerome Lacombe, PhD; Justin Moser, MD; Michael Gordon, MD; David Winkler, PhD; Frederic Zenhausern, PhD, MBA

Introduction:

Effective wound healing remains a global challenge, where chronic, nonhealing wounds persist due to oxidative stress, inflammation, and insufficient angiogenesis. Current strategies often fail to address these overlapping deficits, underscoring the need for innovative therapies¹. As atomic drugs (H₂, Xe) are investigated as potent therapeutic molecules, molecular hydrogen has demonstrated selective antioxidant (Nrf2, SOD, MDA, CAT) and anti-inflammatory (IL-6/10/1β, I-CAM, TNFα) properties^2,3. However, its therapeutic delivery has been largely limited to inhalation, resulting in non-targeted biodistribution.

 

Herein, we introduce a novel gas marble delivery technology, where therapeutic gas is entrapped within a nanoparticle-fortified liquid film, forming stable structures capable of withstanding up to 10× the Laplace pressure. For transdermal delivery to chronic wounds, these “marbles” are formulated into a topical patch. In parallel, this study utilizes a computational pipeline to investigate the interactions of gases with proteins dysregulated in the wound environment to discover new therapeutic capabilities of atomic drugs.

Methods: Biomaterials: Gas marble-entrapped biomaterial gels were formed from 5% alginate/0.5% xanthan gum. Hydrophobic silica nanoparticles (10mg/mL; 14nm diameter) and surfactant (Tween-20 0.1%) were incorporated, followed by sparging with H₂ gas (5sl/m, 25 μm pores, 5min.) and crosslinked with CaCl₂ (1%). Hydrogen concentration was measured by Unisense microsensor.

 
Computational modeling: Protein structures were obtained from RCSB PDB. Non-standard residues and water molecules were removed, hydrogens added, and Gasteiger charges assigned. AutoGrid4 computed Xenon-protein interaction energy maps, and sites with binding energies < 0 kcal/mol were extracted.

Results:

Gas marble–entrapped biomaterials exhibited a cumulative H₂ release (AUC) of ~3,573 µmol-h over 24 h. Franz cell diffusion studies demonstrated ~21.31 μmol-h release (0–6 h vs. 0.0 mM N₂-filled control), implying transdermal compatibility. Fibroblasts treated with H₂-filled marbles under oxidative stress showed a downregulation trend in Nrf-2 pathway genes (SOD1, CAT, HO-1, TXNRD1) and inflammatory markers (IL-6, IL-8, IL-β1), indicative of mitigation of oxidative stress-induced cellular damage. Binding energy calculations predicted Xe interacts with MMP9 (-1.367 - -0.917 kcal/mol), suggesting biological modulation.

Discussion:

Gas marble technology demonstrated potential as a targeted delivery system for chronic wound management. Computationally, the favorable interactions of Xe suggest a new application for Xenon in modulating tissue repair activity.