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Background: Malaria still kills young children in rural endemic areas because early treatment is not available. Thus, the World Health Organization recommends the administration of artesunate suppositories as pre-referral treatment before transportation to the hospital in case of severe symptoms with an unavailable parenteral and oral treatment. However, negative cultural perception of the rectal route, and limited access to artesunate suppositories, could limit the use of artesunate suppositories. There is therefore a need for an alternative route for malaria pre-referral treatment. The aim of this study was to assess the potential of intranasal route for malaria pre-referral treatment.Methods: The permeability of artesunate through human nasal mucosa was tested in vitro. The Transepithelial Electrical Resistance (TEER) of the nasal mucosa was followed during the permeation tests. Beside, regional deposition of artesunate powder was assessed with a unidose drug delivery device in each nostril of a nasal cast. Artesunate quantification was performed using Liquid Chromatography coupled to tandem Mass Spectrometry. Results: The experimental model of human nasal mucosa was successfully implemented. Using this model, artesunate powder showed a much better passage rate through human nasal mucosa than solution (26.8 ± 6.6% versus 2.1 ± 0.3%). More than half (62.3%) of the artesunate dose sprayed in the nostrils of the nasal cast was recovered in the olfactory areas (44.7 ± 8.6%) and turbinates (17.6 ± 3.3%) allowing nose-to-brain and systemic drug diffusion, respectively.Conclusion: Artesunate powder showed a good permeation efficiency on human nasal mucosa. Moreover it can be efficiently sprayed in the nostrils using unidose device to reach the olfactory area leading to a fast nose-to-brain delivery as well as a systemic effect. Taken together, those results are part of the proof-of-concept for the use of intranasal artesunate as a malaria pre-referral treatment.

The complexation of Eu(III) by hydro-soluble degradation products (HDPs) from a radio-oxidized polyesterurethane is investigated. The polyesterurethane Estane 5703® (PURe) is radio-oxidized at 1000 kGy with γ-rays at room temperature. The polymer is then hydrolysed by a simplified artificial cement pore water solution (pH 13.3) for 31 days at 60 °C. The HDPs within the leachate are characterized using gas chromatography-mass spectrometry, ionic chromatography, and TOC analyser. The complexation of Eu(III) is studied by time-resolved luminescence spectroscopy (TRLS). The main HDPs are adipic acid – hexane-1,6-dioic acid – and butane-1,4-diol. Unlike HDPs from non-irradiated PURe, the HDPs from 1000 kGy γ-irradiated PURe do form complexes with Eu(III) at pH 13.3. Neither adipate nor butane-1,4-diol are responsible for this complexation. The existence of several types of complexes is evidenced by TRLS and electrospray ionization mass spectroscopy (ESI-MS): complexation reactions and operational constants are proposed. The complexes formed at high pH (from 10 to 13) are different from the lower pH complexes. The lower pH complexes are studied by ESI-MS and two ligands are identified: adipate and an oligomer.

This work reports the effect of very high doses, up to 10 MGy, on the H2 emission from high density polyethylene (HDPE) irradiated with gamma rays and ion beams, in the presence of oxygen. This was obtained through a two-step procedure. First, HDPE films were pre-aged, at different doses, using either gamma rays or ion beams. In the second step, the pre-aged samples were irradiated in closed glass ampoules for gas quantification, using the same beam type as for pre-ageing. The hydrogen emission rate decreases when dose increases for both gamma rays and ion beams. However, the decreasing rate appears higher under gamma rays than under ion beam irradiations and this is assigned to a lesser oxidation level under the latter. Herein, we show the effectiveness of the radiation-induced defects scavenging effect under oxidative atmosphere, under low and high excitation densities.

The complexing power of hydrosoluble degradation products (HDPs) from an alkaline hydrolysis of a 10 MGy γ-irradiated polyvinylchloride is studied. The complexation of Eu(III), as an analogue of lanthanide and actinide radionuclides at their +III oxidation state for oxygen containing functions, is evidenced both from the increasing of Eu(OH)3(s) dissolution, and from a complexometric titration by time-resolved luminescence spectroscopy. The dissolution of Eu(OH)3(s) in a simplified alkaline solution (0.3 M KOH/0.1 M NaOH) increases moderately, but significantly, with the HDPs concentration. The luminescence signal of the supernatant clearly indicates the presence of several complexed Eu(III) species. Performing a complexometric titration of Eu(III) from pH 6 by alkaline HDPs shows the formation of two different species with increasing HDPs’ concentration and pH. Operational complexation constants – based on dissolved carbon concentration – are proposed. The analyses of the spectra and luminescence decays seem to confirm the presence of two different species.

International audience; In the context of the geological nuclear waste storage, water-soluble products of an industrial poly(ester urethane) are investigated. This polymer was radio-oxidized up to 10 MGy with gamma rays under air at room temperature. The unirradiated and irradiated materials were hydrolyzed for 28 days at 60 C in pure water (MilliQ water). The solutions were characterized using different analytical tools (total organic carbon analyzer, ionic chromatography, gas chromatography coupled with mass spectrometry and tandem mass spectrometry). From 11 to 30 per cent of the water-soluble molecules present in the solutions have been quantified. Most of molecules identified are esters, alcohols, carboxylic acids, diols and ketones. Mechanisms were deduced from the detected molecules. It was observed that the irradiated material was about 70 times more sensitive to hydrolysis than the unirradiated one.