Communication Dans Un Congrès Année : 2025

Zwitterionic chelatant chitosans for oral administration in the context of radioprotection

Thomas Brichart
Ross Berbeco
  • Fonction : Auteur
  • PersonId : 1288724
Laurent David

Résumé

The mitigation of nuclear contamination involves two principal strategies: decorporation agents to extract radionuclides from the body and radioprotective drugs to prevent or reduce the harmful effects of ionizing radiations. Existing approaches, however, face significant limitations: agents like potassium iodide and Prussian blue have narrow activity spectra and restricted timeframes of efficacy, while others, such as Ca-DTPA, require hospital administration, limiting their utility for large-scale deployment. Additionally, systemic administration of decorporating agents often leads to significant side effects. Chitosan, a natural polysaccharide derived from chitin (sourced from crustaceans, cephalopods, or mushrooms), emerges as a promising alternative. It is biocompatible, widely used in food supplements, and exhibits intrinsic reactive oxygen species (ROS) scavenging properties. By functionalizing chitosan with DOTAGA—a chelating agent—we developed a zwitterionic, water-soluble polymer that combines the advantages of the biopolymer with efficient radionuclide traces chelation. The principle is to use a compound that will not pass into the bloodstream after oral administration, and that will be capable of both capturing radionuclides and mitigating the effects of ionizing radiations. In vivo biodistribution confirmed that chitosan@DOTAGA does not cross the intestinal barrier and is rapidly excreted in the feces. Additional experiments demonstrated its potent ROS scavenging capabilities, particularly in radiative environments. In vitro and in vivo assays revealed its capacity to reduce the absorption of heavy metals following oral contamination. Notably, studies in mice highlighted its ability to decorporate natural uranium and attenuate associated inflammatory responses. Moreover, the compound demonstrated promising chelation efficacy towards radioactive isotopes such as 242Pu and 243Am. These encouraging results pave the way for further development of chitosan@DOTAGA, including preclinical evaluations of its effectiveness against a broader range of radionuclides and the formulation of convenient oral dosage forms, such as tablets, for large-scale use in radiological emergencies.

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Dates et versions

hal-05045158 , version 1 (24-04-2025)

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  • HAL Id : hal-05045158 , version 1

Citer

Arthur Durand, Augustin Tillement, Jordyn Ann Howard, Halyna Kuznietsova, Natalia Dziubenko, et al.. Zwitterionic chelatant chitosans for oral administration in the context of radioprotection. RRS 2025 Workshop: Medical Countermeasure R&D in the Radiation Research Community, Radiation Research Society, Apr 2025, San Antonio (TX), United States. ⟨hal-05045158⟩
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