title: Superresolution and Fluorescence Dynamics Evidence Reveal That Intact Liposomes Do Not Cross the Human Skin Barrier.
abstract: In this study we use the combination of super resolution optical microscopy and raster image correlation spectroscopy (RICS) to study the mechanism of action of liposomes as transdermal drug delivery systems in human skin. Two different compositions of liposomes were applied to newly excised human skin, a POPC liposome and a more flexible liposome containing the surfactant sodium cholate. Stimulated emission depletion microscopy (STED) images of intact skin and cryo-sections of skin treated with labeled liposomes were recorded displaying an optical resolution low enough to resolve the 100 nm liposomes in the skin. The images revealed that virtually none of the liposomes remained intact beneath the skin surface. RICS two color cross correlation diffusion measurements of double labeled liposomes confirmed these observations. Our results suggest that the liposomes do not act as carriers that transport their cargo directly through the skin barrier, but mainly burst and fuse with the outer lipid layers of the stratum corneum. It was also found that the flexible liposomes showed a greater delivery of the fluorophore into the stratum corneum, indicating that they functioned as chemical permeability enhancers.
authors.affiliation: Advanced bioimaging group/MEMPHYS Center for membrane biophysics, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
authors.forename: Jes
authors.initials: J
authors.lastname: Dreier
authors.affiliation: Department of reconstructive surgery, Odense University Hospital, Odense, Denmark.
authors.forename: Jens A
authors.initials: JA
authors.lastname: Sørensen
authors.affiliation: Advanced bioimaging group/MEMPHYS Center for membrane biophysics, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Brewer
mesh_terms: D000279:Administration, Cutaneous; D020285:Cryoelectron Microscopy; D004058:Diffusion; D004337:Drug Carriers / Q000493:pharmacokinetics; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000493:pharmacokinetics*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence / Q000379:methods*; D010539:Permeability; D010713:Phosphatidylcholines / Q000737:chemistry; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption
chemical_list: D004337:Drug Carriers; D005456:Fluorescent Dyes; D008081:Liposomes; D010713:Phosphatidylcholines; C028694:1-palmitoyl-2-oleoylphosphatidylcholine