Actinide Decorporation: A Review on Chelation Chemistry and Nanocarriers for Pulmonary Administration

Abstract

Chelation is considered the best method for detoxification by promoting excretion of actinides (Am, Np, Pu, Th, U) from the human body after internal contamination. Chemical agents that possess carboxylic acid or hydroxypyridinonate groups play a vital role in actinide decorporation. In this review article, we provide considerable background details on the chelation chemistry of actinides with an aim to formulate better decorporation agents. Nanocarriers for pulmonary delivery represent an exciting prospect in the development of novel therapies for actinide decorporation that both reduce toxic side effects of the agent and improve its retention in the body. Recent studies have demonstrated the benefits of using a nebulizer or an inhaler to administer chelating agents for the decorporation of actinides. Effective chelation therapy with large groups of internally contaminated people can be a challenge unless both the agent and the nanocarrier are readily available from strategic national stockpiles for radiological or nuclear emergencies. Sunflower lecithin is particularly adept at alleviating the burden of administration when used to form liposomes as a nanocarrier for pulmonary delivery of diethylenetriamine-pentaacetic acid (DTPA) or hydroxypyridinone (HOPO). Better physiologically-based pharmacokinetic models must be developed for each agent in order to minimize the frequency of multiple doses that can overload the emergency response operations.