Paper A NEW FORMULATION CONTAINING CALIXARENE MOLECULES AS AN EMERGENCY TREATMENT OF URANIUM SKIN CONTAMINATION Aure ´lie Spagnul,* † Ce ´line Bouvier-Capely,* Guillaume Phan,* Franc ¸ois Rebie `re,* and Elias Fattal † Abstract—Cutaneous contamination represents the second highest contamination pathway in the nuclear industry. De- spite that the entry of actinides such as uranium into the body through intact or wounded skin can induce a high internal exposure, no specific emergency treatment for cutaneous contamination exists. In the present work, an innovative formulation dedicated to uranium skin decontamination was developed. The galenic form consists in an oil-in-water nano- emulsion, which contains a tricarboxylic calixarene known for its high uranium affinity and selectivity. The physicochemical characterization of this topical form revealed that calixarene molecules are located at the surface of the dispersed oil droplets of the nanoemulsion, being thus potentially available for uranium chelation. It was demonstrated in preliminary in vitro experiments by using an adapted ultrafiltration method that the calixarene nanoemulsion was able to extract and retain more than 80% of uranium from an aqueous uranyl nitrate contamination solution. First ex vivo experiments carried out in Franz diffusion cells on pig ear skin explants during 24 h showed that the immediate application of the calixarene nanoemulsion on a skin contaminated by a uranyl nitrate solution allowed a uranium transcutaneous diffusion decrease of about 98% through intact and excori- ated skins. The calixarene nanoemulsion developed in this study thus seems to be an efficient emergency system for uranium skin decontamination. Health Phys. 99(3):430 – 434; 2010 Key words: contamination; decontamination; skin dose; uranium INTRODUCTION INTERNAL CONTAMINATION of power plant workers by actin- ides may occur by inhalation, ingestion, or penetration through wounds or intact skin. Although the most current contamination pathway is inhalation (Gerber and Thomas 1992), the contamination through intact or wounded skins is still a big concern, since it may induce a high internal exposure of contaminated indi- viduals after translocation of the radionuclides from the contamination site into the body (De Rey et al. 1983; Lopez et al. 2000; Petitot et al. 2004, 2007a and b). The current medical care in case of skin contami- nation only occurs after transfer of the victim to the medical unit of the nuclear site, and it only consists in local decontamination of the wound by rinsing with soaped water or a 25% calcic salt of diethylene triamine pentaacetic acid (Ca-DTPA) solution. This procedure is often followed by a decorporation treat- ment with intravenous injection of 1 g of Ca-DTPA in 4 mL (ASN 2008) to reduce the risks of tissue damage and induction of cancer. A surgical excision of the contaminated tissues can be needed in order to remove residual radionuclides and prevent their penetration into the body (Gerber and Thomas 1992; Bailey et al. 2003). Nevertheless, with Ca-DTPA exhibiting a lack of selectivity and affinity for uranium in biological medium, these procedures are ineffective in case of uranium contamination that may induce strong kidney toxicity (Lopez et al. 2000). Some chelating agents more specific to uranium have been developed in order to decorporate uranium from the body (Durbin 2008). Except for the biphosphonate molecule series (Houpert et al. 2004; Yang et al. 2005; Xu et al. 2008), none of those chelating agents have been used in pharmaceu- tical forms dedicated to skin decontamination. In addition, the specific uranium chelation by the biphos- phonate molecules within the proposed formulations has not been demonstrated. In this context, we have developed a new topical pharmaceutical form dedicated to emergency treatment of uranium skin contamination. We have taken advantage of the particular chelation properties of a calixarene * IRSN, Radiochemistry Laboratory, DRPH/SDI, BP 17 F-92262 Fontenay-aux-Roses, France; † Laboratoire de Physico-chimie Phar- macotechnie et Biopharmacie, Faculte ´ de Pharmacie, F-92296, UMR CNRS 8612, Cha ˆtenay-Malabry, France. For correspondence contact: Ce ´line Bouvier-Capely, IRSN/ DRPH/SDI/LRC, BP 17, F-92262 Fontenay-aux-Roses, France, or email at celine.bouvier@irsn.fr. (Manuscript accepted 27 December 2009) 0017-9078/10/0 Copyright © 2010 Health Physics Society DOI: 10.1097/HP.0b013e3181d1a1b6 430