Background: Chelating agents such as diethylenetriamine pentaacetic acid (DTPA) can be used as a decorporation drug in the zinc (Zn) form to treat internal radioactive contamination after exposure to plutonium or americium in a nuclear accident. Although Zn-DTPA is normally administered intravenously, inhalation of Zn-DTPA in aerosol form is a better route for direct delivery to the lungs. This work investigates the feasibility of synthesizing Zn-DTPA from three common chemicals and aerosolizing it using a jet or ultrasonic nebulizer.
Methods: The particle size distribution (PSD) of this decorporation agent at different concentrations were tested in vitro using two different methods: inertial impaction and aerodynamic time of flight. The particles were generated using either a jet nebulizer or an ultrasonic nebulizer. Two parameters, namely the mass median aerodynamic diameter and the geometric standard deviation, were assessed to determine the PSD of the generated aerosols. These parameters were obtained for different concentrations of Zn-DTPA using both nebulizers.
Results And Conclusions: Zn-DTPA was successfully synthesized for decorporation purposes. Aerosol particles within the inhalable range were successfully generated by both nebulizers from four different concentrations of Zn-DTPA. It was found that the medication concentration did not affect the PSD of Zn-DTPA. The ultrasonic nebulizer was observed to produce a slightly larger aerosol particle size and required slightly longer treatment periods to deliver an effective dose to the lungs when compared with the jet nebulizer. Both nebulizers can be sustainably run to administer the agent for effective decorporation treatment of a large population after any major nuclear accident.
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http://dx.doi.org/10.1089/jamp.2017.1419 | DOI Listing |
Molecules
December 2024
Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Inhalation of aerosolized uranium is recognized as a principal mode of exposure, posing significant risks of damage to the lungs, kidneys, and other vital organs. To enhance nuclide elimination from the body, chelating agents are employed; however, single-component chelators often exhibit limited spectral activity and low effectiveness, resulting in toxicologically relevant concentrations. We have developed a composite chelating agent composed of 3,4,3-Li(1,2-HOPO), DFP, and HEDP in optimized ratios, demonstrating marked improvements in eliminating inhaled uranium.
View Article and Find Full Text PDFRSC Adv
December 2024
School of Safety Science and Emergency Management, Wuhan University of Technology Wuhan 430070 China.
Searching for highly selective, efficient, and low-toxicity chelating agents is central to resolving uranium contamination . Peptides composed of amino acids exhibit very low toxicity for accumulation in the human body and have been proven effective in chelating actinides within the human body. Herein, we report a rationally designed short phosphorylated peptide sequence PP-B, which exhibits high affinity and selectivity for uranyl compared to other trace elements present in the body (such as Na, K, Ca, Co, Fe, Fe, Mg, Mn, Zn).
View Article and Find Full Text PDFAdv Healthc Mater
January 2025
State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Army Medical University, Chongqing, 400038, China.
J Chromatogr A
October 2024
Université Paris-Saclay, CEA, Service de Physico Chimie, Gif-sur-Yvette F-91191, France. Electronic address:
In the field of nuclear toxicology, the knowledge of the interaction of actinides (An) with biomolecules is of prime concern in order to elucidate their toxicity mechanism and to further develop selective decorporating agents. In this work, we demonstrated the great potential of hydrophilic interaction liquid chromatography (HILIC) to separate polar thorium (Th) biomimetic peptide complexes, as a key starting point to tackle these challenges. Th was used as plutonium (Pu) analogue and pS16 and pS1368 as synthetic di- and tetra-phosphorylated peptides capable of mimicking the interaction sites of these An in osteopontin (OPN), a hyperphosphorylated protein.
View Article and Find Full Text PDFPharmaceuticals (Basel)
July 2024
State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China.
Radionuclide uranium has both a chemical and radioactive toxicity, leading to severe nephrotoxicity as it predominantly deposits itself in the kidneys after entering into human bodies. It crosses renal cell membranes, accumulates in mitochondria and causes mitochondrial oxidative damage and dysfunction. In this study, a mitochondria-targeted heptamethine indocyanine small molecule chelator modified with gallic acid (IR-82) is synthesized for uranium detoxication.
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