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Papers of the Week


Papers: 25 Jun 2022 - 1 Jul 2022


Animal Studies


2022 Jun 29


Sci Transl Med


14


651

Delivery of therapeutic carbon monoxide by gas-entrapping materials.

Authors

Byrne JD, Gallo D, Boyce H, Becker SL, Kezar KM, Cotoia AT, Feig VR, Lopes A, Csizmadia E, Longhi M S, Lee J S, Kim H, Wentworth AJ, Shankar S, Lee G R, Bi J, Witt E, Ishida K, Hayward A, Kuosmanen JLP, et al.
Sci Transl Med. 2022 Jun 29; 14(651):eabl4135.
PMID: 35767653.

Abstract

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