10578 DOI: 10.1021/la100691m Langmuir 2010, 26(13), 10578–10584 Published on Web 04/09/2010 pubs.acs.org/Langmuir © 2010 American Chemical Society Application of Bicellar Systems on Skin: Diffusion and Molecular Organization Effects Gelen Rodrı´guez,* ,† Laia Rubio, † Mercedes C ocera, ‡ Joan Estelrich, § Ramon Pons, † Alfonso de la Maza, † and Olga L opez † † Departament de Tecnologia Quı´mica i de Tensioactius, Institut de Quı´mica Avanc -ada de Catalunya (I.Q.A.C), Consejo Superior de Investigaciones Cientı´ficas (C.S.I.C.), C/Jordi Girona 18-26, 08034 Barcelona, Spain, ‡ BM16, European Synchrotron Radiation Facility, Grenoble, France, and § Departamento de Fisicoquı´mica, Facultad de Farmacia, Universidad de Barcelona, Av. Joan XXIII s/n, 08028, Barcelona, Spain Received February 16, 2010. Revised Manuscript Received March 22, 2010 The effect of bicelles formed by dipalmitoylphosphatidylcholine (DPPC)/dihexanoylphosphatidylcholine (DHPC) on stratum corneum (SC) lipids was studied by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy at different temperatures. Analysis of the lipid organization in terms of chain conformational order and lateral packing shows that the use of bicelles hampers the fluidification of SC lipids with temperature and leads to a lateral packing corresponding to a stable hexagonal phase. Grazing incidence small- and wide-angle X-ray scattering (GISAXS and GIWAXS) techniques confirm these results and give evidence of higher lamellar order after treatment with these bicelles. Additionally, the effects of DPPC/DHPC and dimyristoylphosphatidylcholine (DMPC)/DHPC bicelles at different SC depths were compared. The combination of ATR-FTIR spectroscopy and the tape-stripping method was very useful for this purpose. Introduction Bicelles are discoidal aggregates formed in water by a flat bilayer of long chain phospholipids, stabilized by a rim of short chain phospholipids. 1 These structures have the ability to be oriented in magnetic fields, which has permitted their use as membrane models in nuclear magnetic resonance (NMR) studies. 2 Additionally, bicelles have other properties such as avoiding surfactants, modulable structure, and small enough size for skin penetration. For these reasons, these structures are proposed for new applications such as dermatological, cosmetic, and/or pharmaceutical applications. The skin barrier function is mainly due to the specific composi- tion and organization of the outermost part of the epidermis, the stratum corneum (SC). This SC is a very thin layer of flat anucleated cells (the corneocytes) surrounding by a lipid matrix organized in bilayers (the intercellular lipids), which are a mixture composed mainly of ceramides, cholesterol, and fatty acids. 3-5 The molecular organization of the SC lipids has been widely studied, 6,7 and the effect of bicelles on the skin is currently studied by our group. Recently, we reported that changes in the composi- tion and/or gel-to-liquid crystalline phase transition temperature (T m ) of phospholipids building bicelles induce specific effects on the skin barrier function. 8-10 Some of the more useful techniques for these studies are attenuated total reflectance-Fourier transform infrared (ATR- FTIR) spectroscopy and X-ray scattering. The vibrational char- acteristic frequencies of the alkyl chain lipids related to differently ordered phases have been extensively reported by ATR-FTIR. 10-12 Alkyl chain arrangement of the SC lamellar structure exhibits higher order in the gel phase (orthorhombic, OR, and hexagonal, HEX) than in the liquid-crystalline phase (LIQ). The X-ray scattering technique also provides information about the molecular organization of lipids. 13 Small-angle X-ray scattering is used to obtain information about the repeat distance of the lipid lamellar phase, and wide-angle X-ray scattering shows the lateral packing of the lipids. In a recent work 10 we reported useful data on the conformational changes in the SC induced by DMPC/DHPC bicellar systems. These systems caused a phase transition from the gel to the liquid crystalline state in the lipid conformation of SC, a fact probably related to the permeabilizing effect described for the DMPC/DHPC bicelles. 8 Our previous work shows that the inter- action of the bicellar systems with the skin is complex. This complexity is partly based on the versatility of these nanostructures, which have morphologies and structures that are highly sensitive to the thermotropic behavior of the phospholipids. 10 The present work seeks to evaluate the effect of a new bicellar system, DPPC/DHPC, on the SC lipid organization. This new *Corresponding author: e-mail gelen.rodriguez@cid.csic.es; Tel 34-93 400 61 00; Fax 34-93 204 59 04. (1) Sanders, C. R.; Hare, B. J.; Howard, K. P.; Prestegard, J. H. Prog. NMR Spectrosc. 1994, 26, 421–444. (2) Whiles, J. A.; Deems, R.; Vold, R. R.; Dennis, E. A. Bioorg. Chem. 2002, 30, 431–442. 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