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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.

SUBMITTER: Dreier J

PROVIDER: S-EPMC4709185 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Superresolution and Fluorescence Dynamics Evidence Reveal That Intact Liposomes Do Not Cross the Human Skin Barrier.

Dreier Jes J Sørensen Jens A JA Brewer Jonathan R JR

PloS one 20160111 1

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 ...[more]

PMID: 26751684

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Project description:BackgroundThe objective of this study was to measure skin characteristics in premature (PT), late preterm (LPT), and full-term (FT) neonates compared with adults at two times (T1, T2).MethodsSkin samples of 61 neonates and 34 adults were analyzed for protein biomarkers, natural moisturizing factor (NMF), and biophysical parameters. Infant groups were: <34 weeks (PT), 34-<37 weeks (LPT), and ≥37 weeks (FT).ResultsForty proteins were differentially expressed in FT infant skin, 38 in LPT infant skin, and 12 in PT infant skin compared with adult skin at T1. At T2, 40 proteins were differentially expressed in FT infants, 38 in LPT infants, and 54 in PT infants compared with adults. All proteins were increased at both times, except TMG3, S100A7, and PEBP1, and decreased in PTs at T1. The proteins are involved in filaggrin processing, protease inhibition/enzyme regulation, and antimicrobial function. Eight proteins were decreased in PT skin compared with FT skin at T1. LPT and FT proteins were generally comparable at both times. Total NMF was lower in infants than adults at T1, but higher in infants at T2.ConclusionsNeonates respond to the physiological transitions at birth by upregulating processes that drive the production of lower pH of the skin and water-binding NMF components, prevent protease activity leading to desquamation, and increase the barrier antimicrobial properties.ImpactNeonates respond to the transitions at birth by upregulating processes that drive the production of lower pH of the skin and NMF, prevent protease activity leading to desquamation, and increase the antimicrobial properties of the barrier. The neonatal epidermal barrier exhibits a markedly different array of protein biomarkers both shortly after birth and 2-3 months later, which are differentially expressed versus adults. The major biomarker-functional classes included filaggrin processing, protease inhibitor/enzyme regulators, antimicrobials, keratins, lipids, and cathepsins. The findings will guide improvement of infant skin care practices, particularly for the most premature infants with the ultimate goals mitigating nosocomial infection.

Project description:Conjugated polydiacetylene (PDA) possessing stimuli-responsive properties has been intensively investigated for developing efficient sensors. We report here fluorescence resonance energy transfer (FRET) in liposomes synthesized using different molar ratios of dansyl-tagged diacetylene and diacetylene-carboxylic acid monomers. Photopolymerization of diacetylene resulted in cross-linked PDA liposomes. We used steady-state electronic absorption, emission, and fluorescence anisotropy (FA) analysis to characterize the thermal-induced FRET between dansyl fluorophores (donor) and PDA (acceptor). We found that the monomer ratio of acceptor to donor ( R ad) and length of linkers (functional part that connects dansyl fluorophores to the diacetylene group in the monomer) strongly affected FRET. For R ad = 10 000, the acceptor emission intensity was amplified by more than 18 times when the liposome solution was heated from 298 to 338 K. A decrease in R ad resulted in diminished acceptor emission amplification. This was primarily attributed to lower FRET efficiency between donors and acceptors and a higher background signal. We also found that the FRET amplification of PDA emissions after heating the solution was much higher when dansyl was linked to diacetylene through longer and flexible linkers than through shorter linkers. We attributed this to insertion of dansyl in the bilayer of the liposomes, which led to an increased dansyl quantum yield and a higher interaction of multiple acceptors with limited available donors. This was not the case for shorter and more rigid linkers where PDA amplification was much smaller. The present studies aim at enhancing our understanding of FRET between fluorophores and PDA-based conjugated liposomes. Furthermore, receptor tagged onto PDA liposomes can interact with ligands present on proteins, enzymes, and cells, which will produce emission sensing signal. Therefore, using the present approach, there exist opportunities for designing FRET-based highly sensitive and selective chemical and biochemical sensors.

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Superresolution and Fluorescence Dynamics Evidence Reveal That Intact Liposomes Do Not Cross the Human Skin Barrier.

Publications

Superresolution and Fluorescence Dynamics Evidence Reveal That Intact Liposomes Do Not Cross the Human Skin Barrier.

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