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 been shown to be of low specificity, and their effectiveness remains modest. The main health risk resulting from internal contamination is irradiation of the target organs for retention of 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 marketing authorisation and whose complexation properties with divalent cations are strongly suspected. The first step consisted of assessing the affinity of BP molecules with the cations of interest. To this end, we set up an analytical method based on capillary electrophoresis. Several charged metal-ligand complexes have been identified. During the next step, we developed new liposomal formulations to deliver strontium/cobalt potential chelating agents to the main radionuclide retention organs (bone, liver, and kidneys). In vivo evaluation of the decorporation efficiencies of both free and liposome-encapsulated molecule were then 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. The results obtained thus highlight the need to continue efforts to find an effective, efficient chelating treatment and the importance of taking care of victims as soon as possible after exposure
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