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Drug Delivery

Drug Delivery - Poster Session E

W2 - Gas Marble Therapeutics for the Treatment of Chronic Wounds

Saturday, October 11, 2025
10:00 AM - 11:00 AM PDT
Location: Exhibit Hall F, G & H

Introduction: : Effective wound healing remains a global clinical challenge, where chronic, nonhealing wounds persist due to overlapping deficits in oxidative stress, inflammation, and insufficient angiogenesis, resulting in barrier dysfunction [1]. Current strategies for chronic wound management are inefficient as they fail to address the multifaceted repair process, and innovative therapies are needed to improve outcomes. As gaseous molecules have been increasingly explored for wound care, molecular hydrogen (H2) has been demonstrated to be a powerful antioxidant, reducing ROS, modulating inflammation (IL-6/10/1β, ICAM-1, TNFα), and tempering oxidative stress (Nrf2, MDA, SOD, CAT) [2,3]. Yet, the translation of gas therapeutic delivery has been limited to inhalation, which results in non-targeted delivery and low biodistribution. To address this challenge, we introduce a novel gas marble technology, where therapeutic gas is entrapped within a liquid film fortified by nanoparticles. These robust structures oppose escaping gas up to 10X the Laplace pressure, making them so stable that they are termed “gas marbles.” Herein, we demonstrate the use of this technology to deliver a targeted treatment (H2) for chronic wound management.

Materials and

Methods: : Gas marble-entrapped biomaterial gels (Fig. 1A-B) were formed from 5% alginate/0.5% xanthan gum. Hydrophobic silica nanoparticles (10mg/mL; 500nm diameter) and surfactant (Tween-20 0.1%) were added, followed by hydrogen gas (5sl/m) by sparger (10um pore size) for 5 min. Finally, gels were crosslinked with CaCl2 (1%). Materials were investigated for diffusion permeability using Franz cell technology with H2 sensor (Unisense) and in vitro by human dermal fibroblast cells (ATCC-BJ) exposed to oxidative stress (800 µM H2O2).

Results, Conclusions, and Discussions::

Results: Gas release kinetics showed gas marble-entrapped biomaterials delivered a peak concentration of 3.8 µmol of H2 at 1 h, with an estimated cumulative release (AUC) of ~32.36 µmol-h of H2 over 24 h, indicating an initial burst release and a sustained delivery phase. To demonstrate that these materials can be used as a drug delivery system, we employed Franz cell technology to assess in vitro drug release. H2-dosed materials were loaded into the donor chamber; samples withdrawn from the receptor chamber (0-6 h timepoints) showed a release of ~21.31 µmol-h (compared to 0.0 mM for control (air-filled)) (Fig 1C), suggesting gas release in the therapeutic range by gas marbles across the synthetic barrier (cellulose). Finally, normal human fibroblast cells exposed to oxidative stress (800 uM 1 h) and H2-filled marbles showed a downregulation trend in the gene expression of the Nrf-2 antioxidant defense pathway (SOD1, CAT, HO-1, TXNRD1) (Fig 1D) and inflammation levels (IL-6, IL-8, ILβ1) (Fig 1E), suggesting that H2-filled gas marble materials have a mitigating effect against oxidative stress-induced cellular damage.


Conclusions: Gas marble technology holds promise as a targeted delivery system for managing chronic wounds. Further studies will evaluate the in vivo efficacy and expand to additional therapeutic gases (e.g., NO for angiogenesis; CO for anti-microbial activity) to advance multifactorial wound therapies.

Acknowledgements and/or References (Optional): : Acknowledgement of Support: This research was funded by the NIAID (NIH), Honor Health Research Institute, and the BIO5 Institute (University of Arizona). We additionally thank the Center for Applied NanoBioscience and Medicine for their ongoing support.

References:
1) Pastar I, Balukoff NC, Marjanovic J, Chen VY, Stone RC, Tomic-Canic M. Molecular Pathophysiology of Chronic Wounds: Current State and Future Directions. Cold Spring Harb Perspect Biol. 2023 Apr 3;15(4):a041243.https://doi.org/10.1101/cshperspect.a041243
2) Zhao, P., Dang, Z., Liu, M. et al. Molecular hydrogen promotes wound healing by inducing early epidermal stem cell proliferation and extracellular matrix deposition. Inflamm Regener 43, 22 (2023). https://doi.org/10.1186/s41232-023-00271-9
3) Li, Y., Shen, C., Zhou, X., Zhang, J., Lai, X., & Zhang, Y. (2022). Local Treatment of Hydrogen-Rich Saline Promotes Wound Healing In Vivo by Inhibiting Oxidative Stress via Nrf-2/HO-1 Pathway. Oxidative medicine and cellular longevity, 2022, 2949824. https://doi.org/10.1155/2022/2949824