Development of Nanocarrier‐Based Oral Pegfilgrastim Formulations for Mitigating Hematopoietic Acute Radiation Syndrome

Abstract The increasing risks of ionizing radiation (IR) from deep space travel and nuclear accidents necessitate the development of effective countermeasures. Acute radiation syndrome (ARS), particularly hematopoietic ARS (H‐ARS), leads to life‐threatening anemia and bone marrow failure, with long‐term risks including cancer and cardiovascular disease. This study presents phenylboronic acid‐functionalized chitosan‐polyethylenimine (CPB) polymers designed for efficient oral delivery of pegfilgrastim (PF), an FDA‐approved radioprotective agent. Nanoparticles are prepared through complexation of PF with tannic acid, forming a negatively charged core, followed by encapsulation with a CPB polymer shell. This supramolecular strategy enables efficient protein condensation into uniform nanoparticles. The nanosystem effectively reduces H‐ARS‐associated anemia in mice by promoting blood cell reconstitution, supported by in vitro results with human hematopoietic stem/progenitor cells. Additionally, the material reduces toll‐like receptor activation in multiple human cell types post‐radiation. This system may mitigate radiation injury risks from accidental exposure on Earth and during extended space missions.