Evaluation of PEG-BPEI as a potential mitigator against gastrointestinal acute radiation syndrome

ABSTRACT Gastrointestinal (GI) toxicity remains a significant contributor to mortality following exposure to ionizing radiation (IR), leading to a severe condition known as GI Acute Radiation Syndrome (GI-ARS). The lack of effective treatments for GI-ARS has underscored the urgent need for development of medical countermeasures (MCMs) to mitigate its devastating effects. To address this unmet medical need, we have developed a murine model of partial body irradiation (PBI) that simulates a scenario GI injury is created while a small portion of hematopoietic system is spared. This model allows us to study the specific effects of radiation on the GI tract while minimizing systemic toxicity. Using a clinical linear accelerator, we have determined the LD50/30, the lethal dose of radiation that kills 50% of the animals within 30 days, for both male and female mice in this model. This LD50/30 serves as a critical benchmark for evaluating the efficacy of potential MCMs. Given the ability of PEG-BPEI to combat bacterial infections by killing both Gram-positive and Gram-negative bacteria, disabling antibiotic resistance mechanisms, neutralizing endotoxins, and dispersing biofilms, we hypothesize that it can mitigate leaky gut post-radiation. By reducing the burden of infection, PEG-BPEI may enhance GI tissue repair, reduce inflammation, and ultimately improve survival rates in mice exposed to ionizing radiation.