Enhanced decorporation of plutonium by DTPA encapsulated in small PEG-coated liposomes

Phan, Guillaume; Gall, B. Le; Grillon, G.; Rouit, E.; Fouillit, M.; Bénech, Henri; Fattal, Elias; Deverre, Jean-Robert

doi:10.1016/j.biochi.2006.06.010

Cited by 22 publications

(11 citation statements)

References 20 publications

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“…However, although some of these chelators were promising, none has proved effective enough or without side effects to replace DTPA as the treatment of choice after Pu contamination. One strategy to improve the efficacy of actinide chelation is to modify the formulation of DTPA with the constraint of using DTPA, such as the encapsulation of DTPA in liposomes to enhance its biological period or to target the liver (15,16). Another strategy is the local delivery of the chelator at the primary site of contamination (lungs or wound).…”

Section: Introductionmentioning

confidence: 99%

Decorporation Approach Following Rat Lung Contamination with a Moderately Soluble Compound of Plutonium Using Local and Systemic Ca-DTPA Combined Chelation

et al. 2012

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Decorporation efficacy of prompt pulmonary delivery of DTPA dry powder was assessed following lung contamination with plutonium nitrate and compared to an intravenous injection of DTPA solution and a combined administration of both DTPA compounds. In addition, efficacy of a delayed treatment was assessed. In case of either early or late administration, insufflated DTPA was more efficient than intravenously injected DTPA in reducing the plutonium lung burden due to its high local concentration. Prompt treatment with DTPA powder was also more effective in limiting extrapulmonary deposits by removing the early transportable fraction of plutonium from lungs prior its absorption into blood. Translocation of DTPA from lungs to blood may also contribute to the decrease in extrapulmonary retention, as shown by reduced liver deposit after delayed pulmonary administration of DTPA. Efficacy of DTPA dry powder was further increased by the combined intravenous administration of DTPA solution for reducing extrapulmonary deposits of plutonium and promoting its urinary excretion. According to our results, the most effective treatment protocol for plutonium decorporation was the early pulmonary delivery of DTPA powder supplemented by an intravenous injection of DTPA solution. Following inhalation of plutonium as nitrate chemical form, this combined chelation therapy should provide a more effective method of treatment than conventional intravenous injection alone. At later stages following lung contamination, pulmonary administration of DTPA should also be considered as the treatment of choice for decreasing the lung burden.

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Section: Introductionmentioning

confidence: 99%

Decorporation Approach Following Rat Lung Contamination with a Moderately Soluble Compound of Plutonium Using Local and Systemic Ca-DTPA Combined Chelation

et al. 2012

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“…Taking into account the interfacial properties of calixarene molecules, we have developed an oil‐in‐water (O/W) nanoemulsion. Nanoscale systems have already been developed for detoxification therapy17, 18 and for actinides decorporation,19 but they have never been applied to radionuclides skin decontamination. In this article, the physicochemical properties of the calixarene nanoemulsion have been characterized and its efficiency for uranium extraction has been evaluated.…”

Section: Introductionmentioning

confidence: 99%

Calixarene‐Entrapped Nanoemulsion for Uranium Extraction from Contaminated Solutions

Spagnul

Bouvier‐Capely

Phan

et al. 2010

Journal of Pharmaceutical Sciences

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“…Further pharmacokinetic and decorporation studies are warranted in order to determine optimal therapeutic dose levels, possible combined administration given the potential indications about assessing different systemic pools, and timing of treatment, as well as to evaluate which additional radionuclides these drugs might be effective for. For example, a potential avenue for improving the efficacy of the studied chelators might involve the use of vectors or liposomes; a similar approach was applied to plutonium decorporation with DTPA and liposomes (Phan et al 2006).…”

Section: Resultsmentioning

confidence: 99%

EVALUATION OF CUPRIMINE® AND SYPRINE® FOR DECORPORATION OF 60Co AND 210Po

Levitskaia¹,

Creim²,

Curry³

et al. 2010

Health Physics

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The acknowledged risk of deliberate release of radionuclides into local environments by terrorist activities has prompted a drive to improve novel materials and methods for removing internally deposited radionuclides. These decorporation treatments will also benefit workers in the nuclear industry, should an exposure occur. Cuprimine and Syprine are oral therapeutics based on the active ingredients D-penicillamine and N,N'-bis-(2-aminoethyl)-1,2-ethanediamine dihydrochloride, respectively. These therapeutic drugs have been used for several decades to treat Wilson's disease, a genetic defect leading to copper overload, by chelation and accelerated excretion of internally deposited copper. Studies were undertaken to evaluate these FDA-approved drugs for the in vivo decorporation of radioactive cobalt (Co) and polonium (Po) using male Wistar-Han rats. In these studies, Co or Po was administered to animals by IV injection, followed by oral gavage doses of either Cuprimine or Syprine. Control animals received the radionuclide alone. For Co studies, animals received a single dose of Cuprimine or Syprine, while for Po studies animals were repeatedly dosed at 24-h intervals for a total of 5 doses. Results show that Syprine significantly increased urinary elimination and skeletal concentrations of Co compared to controls. While Cuprimine had little effect on total excretion of Co, the skeletal, kidney, liver, muscle, and stomach tissues had significantly lower radioactivity compared to control animals. The low overall excretion of Po made it difficult to reliably measure urinary or fecal radioactivity and draw a definitive conclusion on the effect of Cuprimine or Syprine treatment on excretion. However, Cuprimine treatment was effective at reducing spleen levels of Po compared to controls. Similarly, Syprine treatment produced statistically significant reductions of Po in the spleen and skeletal tissues compared to control animals. Based on these promising findings, further studies to evaluate the dose-response pharmacokinetic profiles for decorporation are warranted.

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Enhanced decorporation of plutonium by DTPA encapsulated in small PEG-coated liposomes

Cited by 22 publications

References 20 publications

Decorporation Approach Following Rat Lung Contamination with a Moderately Soluble Compound of Plutonium Using Local and Systemic Ca-DTPA Combined Chelation

Decorporation Approach Following Rat Lung Contamination with a Moderately Soluble Compound of Plutonium Using Local and Systemic Ca-DTPA Combined Chelation

Calixarene‐Entrapped Nanoemulsion for Uranium Extraction from Contaminated Solutions

EVALUATION OF CUPRIMINE® AND SYPRINE® FOR DECORPORATION OF 60Co AND 210Po

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