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Fluidization of a Dipalmitoyl Phosphatidylcholine Monolayer by Fluorocarbon Gases: Potential Use in Lung Surfactant Therapy

Frédéric Gerber ^* , Marie Pierre Krafft ^*, Thierry F. Vandamme , Michel Goldmann  and Philippe Fontaine  

^* Systèmes Organisés Fluorés à Finalités Thérapeutiques (SOFFT), Institut Charles Sadron (UPR CNRS 22), 67083 Strasbourg Cedex, France; Laboratoire de Chimie Bioorganique (UMR CNRS 7514), Université Louis Pasteur, 67401 Illkirch, France; Institut des NanoSciences de Paris (INSP), Campus Boucicaut, 75015 Paris, France; and Synchrotron SOLEIL, l'Orme des Merisiers, Saint Aubin, BP 48 91192 Gif-sur-Yvette Cedex, France

Correspondence: Address reprint requests to Dr. Marie Pierre Krafft, Institut Charles Sadron (CNRS, UPR 22), 6 rue Boussingault, 67083 Strasbourg Cedex, France. Tel.: 33-3-88-41-40-60; Fax: 33-3-88-41-40-99. E-mail: krafft{at}ics.u-strasbg.fr.

Fluorocarbon gases (gFCs) were found to inhibit the liquid-expanded (LE)/liquid-condensed (LC) phase transition of dipalmitoyl phosphatidylcholine (DPPC) Langmuir monolayers. The formation of domains of an LC phase, which typically occurs in the LE/LC coexistence region upon compression of DPPC, is prevented when the atmosphere above the DPPC monolayer is saturated with a gFC. When contacted with gFC, the DPPC monolayer remains in the LE phase for surface pressures lower than 38 mN m^–1, as assessed by compression isotherms and fluorescence microscopy (FM). Moreover, gFCs can induce the dissolution of preexisting LC phase domains and facilitate the respreading of the DPPC molecules on the water surface, as shown by FM and grazing incidence x-ray diffraction. gFCs have thus a highly effective fluidizing effect on the DPPC monolayer. This gFC-induced fluidizing effect was compared with the fluidizing effect brought about by a mixture of unsaturated lipids and proteins, namely the two commercially available lung surfactant substitutes, Curosurf and Survanta, which are derived from porcine and bovine lung extracts, respectively. The candidate FCs were chosen among those already investigated for biomedical applications, and in particular for intravascular oxygen transport, i.e., perfluorooctyl bromide, perfluorooctylethane, bis(perfluorobutyl)ethene, perfluorodecalin, and perfluorooctane. The fluidizing effect is most effective with the linear FCs. This study suggests that FCs, whose biocompatibility is well documented, may be useful in lung surfactant substitute compositions.