Liposomal formulations of bisphosphonate molecules for the treatment of internal strontium/cobalt contamination
Résumé
In the event of nuclear/radiological incidents or accidents involving internal contaminations with radioactive cobalt or strontium compounds, the current recommended therapeutic options (calcium salts of DTPA and calcium gluconate respectively) have shown low specificity and efficacy. The main health risk resulting from internal contamination is irradiation of the organs accumulating the radionuclides considered (skeleton, liver, kidney), which can cause long-term deleterious effects that can lead to the development of malignant diseases. There is therefore a crucial need to develop new decorporation agents to improve the medical care of patients exposed to such events.
To address this question, the experimental strategy adopted was to use a class of pharmaceutical molecules (Biphosphonates or BPs) that already have regulatory approval and whose complexation properties towards divalent cations have been already shown. The first step of this work consisted of assessing the affinity of BP molecules with the cations of interest (cobalt and strontium). To this end, we set up an analytical method based on capillary electrophoresis. Several charged metal-ligand complexes were identified between cobalt and EHBP. We then developed new liposomal formulations to target these potential chelating molecules to the main radionuclide retention organs (bone, liver, and kidneys). In vivo evaluation of the decorporation efficiencies of both free and liposome-encapsulated molecules were performed in a rodent model. The results showed a clear interaction between the radionuclides and the ligand and unexpected data concerning reference treatments. For now, BP-based treatments do not fulfil all the necessary conditions to constitute a decorporating agent. Thus, our results highlight the need to continue efforts to find an efficient chelating treatment and the importance of starting the treatment as soon as possible after exposure.
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Licence : Copyright (Tous droits réservés)
Licence : Copyright (Tous droits réservés)