Compared in vivo efficiency of nanoemulsions unloaded and loaded with calixarene and soapy water in the treatment of superficial wounds contaminated by uranium.

No emergency decontamination treatment is currently available in the case of radiological skin contamination by uranium compounds. First responders in the workplace or during an industrial nuclear accident must be able to treat internal contamination through skin. For this purpose, a calixarene nanoemulsion was developed for the treatment of intact skin or superficial wounds contaminated by uranium, and the decontamination efficiency of this nanoemulsion was investigated in vitro and ex vivo. The present work addresses the in vivo decontamination efficiency of this nanoemulsion, using a rat model. This efficiency is compared to the radio-decontaminant soapy water currently used in France (Trait rouge®) in the workplace. The results showed that both calixarene-loaded nanoemulsion and non-loaded nanoemulsion allowed a significant decontamination efficiency compared to the treatment with soapy water. Early application of the nanoemulsions on contaminated excoriated rat skin allowed decreasing the uranium content by around 85% in femurs, 95% in kidneys and 93% in urines. For skin wounded by microneedles, mimicking wounds by microstings, nanoemulsions allowed approximately a 94% decrease in the uranium retention in kidneys. However, specific chelation of uranium by calixarene molecules within the nanoemulsion was not statistically significant, probably because of the limited calixarene-to-uranium molar ratio in these experiment conditions. Moreover, these studies showed that the soapy water treatment potentiates the transcutaneous passage of uranium, thus making it bioavailable, in particular when the skin is superficially wounded.

Ex vivo uranium decontamination efficiency on wounded skin and in vitro skin toxicity of a calixarene-loaded nanoemulsion.

The present work aims at studying the decontamination efficacy of a calixarene-loaded nanoemulsion on two ex vivo wounded skin models mimicking superficial stings or cuts contaminated with uranium, and on a third model using excoriation. The decontaminating formulation was compared with the currently used radio-decontaminating soapy water (Trait rouge®) treatment. Moreover, to assess skin damage potentially induced by the undiluted nanoemulsion, in vitro toxicity studies were conducted on an in vitro reconstructed human epidermis, coupled with three different toxicity tests [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide, lactate dehydrogenase, and interleukin-1-α]. This work demonstrated not only a significant decontamination activity of the calixarene nanoemulsion on wounded skin, ranging from 92% to 94% of the applied uranium solution according to the ex vivo model used, but also the absence of side effects of this promising treatment.