Delivery of therapeutic carbon monoxide by gas-entrapping materials

• DOI: 10.1126/scitranslmed.abl4135
• Publication Date: 2022-06-29T17:53:46Z
• Authors: James D. Byrne; David Gallo; Hannah Boyce; Sarah L. Becker; Kristi M. Kezar; Alicia T. Cotoia; Vivian R. Feig; Aaron Lopes; Eva Csizmadia; Maria Serena Longhi; Jung Seung Lee; Hyunjoon Kim; Adam J. Wentworth; Sidharth Shankar; Ghee Rye Lee; Jianling Bi; Emily Witt; Keiko Ishida; Alison Hayward; Johannes L. P. Ku...; Josh Jenkins; Jacob Wainer; Aya Aragon; Kaitlyn Wong; Christoph Steiger; William R. Jeck; Dustin E. Bosch; Mitchell C. Coleman; Douglas R. Spitz; Michael Tift; Robert Langer; Leo E. Otterbein; Giovanni Traverso
• Keywords: Inflammation; 0301 basic medicine; Carbon Monoxide; 03 medical and health sciences; Swine; 615; 610; Animals; Gases; Colitis; Inflammatory Bowel Diseases; 3. Good health

Carbon monoxide (CO) has long been considered a toxic gas but is now recognized bioactive gasotransmitter with potent immunomodulatory effects. Although inhaled CO currently under investigation for use in patients lung disease, this mode of administration can present clinical challenges. The capacity to deliver directly and safely the gastrointestinal (GI) tract could transform management diseases affecting GI mucosa such as inflammatory bowel disease or radiation injury. To address unmet need, inspired by molecular gastronomy techniques, we have developed family gas-entrapping materials (GEMs) delivery tract. We show highly tunable CO, achieving clinically relevant concentrations vivo rodent swine models. support potential range applications foam GEMs, evaluated system three distinct that GEM containing dose-dependently reduced acetaminophen-induced hepatocellular injury, dampened colitis-associated inflammation oxidative tissue mitigated radiation-induced gut epithelial damage rodents. Collectively, GEMs paradigm-shifting implications safe therapeutic across indications.