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

Jes Dreier,Jonathan R Brewer,Jens A Sørensen,Hélder A Santos

doi:10.1371/journal.pone.0146514

Jes Dreier, Jonathan R Brewer + Show 2 more

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https://doi.org/10.1371/journal.pone.0146514

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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.

Highlights

Successful transdermal drug delivery is hindered by the inability of most drugs to penetrate the skin barrier at therapeutically beneficial rates [1, 2]
We have investigated the penetration of POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocoline) large unilamellar vesicles (LUVs) and a flexible vesicle (FLUVs) in human skin using CC-raster image correlation spectroscopy (RICS) of two color fluorescently labeled liposomes and Stimulated emission depletion microscopy (STED) microscopy to investigate whether the intact vesicles penetrate into the skin or if they break upon contact with the skin
Intact skin samples labelled from the stratum corneum (SC) side with free dye before sectioning were investigated using STED

Summary

Introduction

Successful transdermal drug delivery is hindered by the inability of most drugs to penetrate the skin barrier at therapeutically beneficial rates [1, 2]. Very few drugs can cross the skin barrier, and permeability enhancers are needed in order to facilitate transdermal delivery. To advance the development of efficient permeability enhancers, a thorough knowledge of each enhancer’s efficiency and mechanism of action is needed. One of the lipid vesicle candidates for transdermal drug delivery is liposomes or large unilamellar vesicles (LUVs). They are widely used in the cosmetic industry and have been proposed as vehicles to transport and deliver drugs through the skin barrier [7,8,9].

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