Hydrogen sulfide (H₂S) is an endogenously produced gasotransmitter with untapped potential as a therapeutic in the treatment of various diseases and disorders, such as Parkinson's disease, inflammation, cancer, and ischemia-reperfusion injury. Due to its profound antioxidant and anti-inflammatory effects, H₂S plays an important role in regulating angiogenesis, a crucial aspect of healthy wound healing. Transdermal H₂S delivery could enable more efficient and successful healing of difficult-to-treat wounds such as those resulting from diabetic complications. However, current small molecule H₂S donors suffer from limited control over H₂S delivery and often lead to the production of undesirable side products. Here, we demonstrate that H₂S release from metal-organic frameworks (MOFs) is a more promising alternative for controlled transdermal delivery of gaseous H₂S. In particular, we evaluate the stability of a range of MOFs toward H₂S and determine their cytotoxicity toward HeLa cells. From gas adsorption measurements and powder X-ray diffraction studies, we determine that the open-metal site MOF Mg-MOF-74 is best suited for transdermal H₂S delivery due to its strong, reversible binding of the gas as well as its biocompatible nature. In addition to its high capacity for H₂S, the strong interaction between the Lewis basic H₂S and the Lewis acidic Mg²⁺ sites in the framework enable particularly slow exchange of H₂S for water vapor in air, making this material an excellent candidate for transdermal delivery. Last, we demonstrate that H₂S can be transdermally delivered through porcine skin via a Franz cell apparatus significantly longer than an equivalent amount of the commonly used sodium sulfide. From our findings, we conclude that H₂S-loaded MOFs are easily accessible, solid-state sources of H₂S, enabling safe storage and delivery of the gas for use as a wound-healing agent.

Piyusha Lotlikar

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