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BackgroundDoxorubicin and other anthracyclines are crucial cancer treatment drugs. However, they are associated with significant cardiotoxicity, severely affecting patient care and limiting dosage and usage. Previous studies have shown that low carbon monoxide (CO) concentrations protect against doxorubicin toxicity. However, traditional methods of CO delivery pose complex challenges for daily administration, such as dosing and toxicity. To address these challenges, we developed a novel oral liquid drug product containing CO (HBI‐002) that can be easily self‐administered by patients with cancer undergoing doxorubicin treatment, resulting in CO being delivered through the upper gastrointestinal tract. Methods and ResultsHBI‐002 was tested in a murine model of doxorubicin cardiotoxicity in the presence and absence of lung or breast cancer. The mice received HBI‐002 twice daily before doxorubicin administration and experienced increased carboxyhemoglobin levels from a baseline of ≈1% to 7%. Heart tissue from mice treated with HBI‐002 had a 6.3‐fold increase in CO concentrations and higher expression of the cytoprotective enzyme heme oxygenase‐1 compared with placebo control. In both acute and chronic doxorubicin toxicity scenarios, HBI‐002 protected the heart from cardiotoxic effects, including limiting tissue damage and cardiac dysfunction and improving survival. In addition, HBI‐002 did not compromise the efficacy of doxorubicin in reducing tumor volume, but rather enhanced the sensitivity of breast 4T1 cancer cells to doxorubicin while simultaneously protecting cardiac function. ConclusionsThese findings strongly support using HBI‐002 as a cardioprotective agent that maintains the therapeutic benefits of doxorubicin cancer treatment while mitigating cardiac damage. 

Wound healing presents a unique challenge for patients with diabetes. Gas therapies have gained significant attention in the wound-healing community. Carbon monoxide (CO) is a small molecule that is well known for its immune-modulating properties when administered at sublethal concentrations. CO is currently in clinical trials for lung disease, sickle cell anemia, and organ transplantation. Here, we investigated the effects of CO in an in vitro wound-healing model and subsequently developed and tested CO gas-entrapping materials (CO-GEMs) for topical application on wounds to promote healing. In this study, we report the efficacy of CO-GEMs in treating full-thickness wounds and pressure ulcers in diabetic mouse models. Collectively, our findings demonstrate that these novel gas entrapping materials could serve as an alternative therapy to both protect the wound bed and promote healing and replace bulky hyperbaric chambers, standard gauze wound dressings, or expensive skin grafts. 

COoking with gas Low concentrations of carbon monoxide (CO) have shown therapeutic benefit in preclinical models, but safe delivery of appropriate dose has been challenging to achieve. Here, inspired by molecular gastronomy, Byrne et al . designed gas-entrapping materials (GEMs) using components generally recognized as safe, including xanthan gum, methylcellulose, maltodextrin, and corn syrup. Solid, hydrogel, and foam GEMs containing CO could deliver different concentrations of the gas to healthy rodents and pigs through noninhaled routes. In rodent models of colitis, acetaminophen overdose, and radiation-induced proctitis, rectally administered foam GEMs reduced tissue injury and inflammation. Foam GEMs could help achieve safe therapeutic CO delivery.