Liposomal formulations of new decorporation molecules for the treatment of internal Strontium/Cobalt contaminations - IRSN - Institut de radioprotection et de sûreté nucléaire Accéder directement au contenu
Communication Dans Un Congrès Année : 2022

Liposomal formulations of new decorporation molecules for the treatment of internal Strontium/Cobalt contaminations

Résumé

Nuclear/radiological incidents or accidents involving internal contaminations with radioactive cobalt or strontium compounds occur regularly. In this case, the current recommended therapeutic options (calcium salts of DTPA and cobalt gluconate in case of internal cobalt contamination and ammonium chloride and calcium gluconate in case of internal strontium contamination) are of low specificity, and their effectiveness remains modest. There is therefore a crucial need to design new modalities of administration and/or new molecules based on drug discovery or already marketed drugs for decorporation. Our team is developing new liposomal formulations to deliver strontium/cobalt potential chelating agents to the main radionuclide retention organs. In a first step, we have identified and selected bisphosphonates (BP) molecules that can form stable complexes with cobalt and strontium. For that purpose, we have developed different approaches such as UV/Visible spectrophotometry and ion chromatography coupled with ICP-MS detection to screen our preselected candidates. These techniques have enabled the effective visualization of the BPs and divalent cations but compelling detections of BP-metal complexes have yet to be achieved. Additionally, we are currently developing a new separative analytical method based on capillary electrophoresis that should also be very useful for characterizing complexes. The further step will be to encapsulate the candidate molecule into liposomes that will be surface functionalized with specific targeting ligands. The molecular targeting should induce a preferential accumulation of the liposomes in the bone compartments as well as in the liver and kidneys, thus enhances the distribution of the BPs in these key radionuclide retention organs. In vivo evaluation of the decorporation efficiencies of both the free and liposome-encapsulated molecule will then be performed in a rodent model.
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Dates et versions

irsn-04426460 , version 1 (30-01-2024)

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  • HAL Id : irsn-04426460 , version 1

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Geraldine Landon, Guillaume Phan, François Fay, Céline Bouvier-Capely, Elias Fattal. Liposomal formulations of new decorporation molecules for the treatment of internal Strontium/Cobalt contaminations. International Conference on Individual Monitoring of Ionising Radiation (IM2022) and Neutron and Ion Dosimetry Symposium (NEUDOS-14), Apr 2022, Cracovie, Poland. ⟨irsn-04426460⟩
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