Imaging and quantifying drug delivery in skin - Part 2: Fluorescence andvibrational spectroscopic imaging methods.

Understanding the delivery and diffusion of topically-applied drugs on human skin is of paramount importance in both pharmaceutical and cosmetics research. This information is critical in early stages of drug development and allows the identification of the most promising ingredients delivered at optimal concentrations to their target skin compartments. Different skin imaging methods, invasive and non-invasive, are available to characterize and quantify the spatiotemporal distribution of a drug within ex vivo and in vivo human skin. The first part of this review detailed invasive imaging methods (autoradiography, MALDI and SIMS). This second part reviews non-invasive imaging methods that can be applied in vivo: i) fluorescence (conventional, confocal, and multiphoton) and second harmonic generation microscopies and ii) vibrational spectroscopic imaging methods (infrared, confocal Raman, and coherent Raman scattering microscopies). Finally, a flow chart for the selection of imaging methods is presented to guide human skin ex vivo and in vivo drug delivery studies.

Imaging and quantifying drug delivery in skin - Part 1: Autoradiography and mass spectrometry imaging.

In this two-part review we present an up-to-date description of different imaging methods available to map the localization of drugs on skin as a complement of established ex-vivo absorption studies. This first part deals with invasive methods which are grouped in two classes according to their underlying principles: i) methods using radioactivity such as autoradiography and ii) mass spectrometry methods such as MALDI and SIMS. For each method, a description of the principle is given along with example applications of imaging and quantifying drug delivery in human skin. Thanks to these techniques a better assessment of the fate of drugs is obtained: its localization on a particular skin structure, its potential accumulation, etc. A critical comparison in terms of capabilities, sensitivity and practical applicability is included that will help the reader to select the most appropriate technique depending on the particular problem to be solved.

Early use of PbS nanotechnology for an ancient hair dyeing formula.

Lead-based chemistry was initiated in ancient Egypt for cosmetic preparation more than 4000 years ago. Here, we study a hair-dyeing recipe using lead salts described in text since Greco-Roman times. We report direct evidence about the shape and distribution of PbS nanocrystals that form within the hair during blackening. It is remarkable that the composition and supramolecular organization of keratins can control PbS nanocrystal growth inside a hair.

In-situ imaging mass spectrometry analysis of melanin granules in the human hair shaft.

The elemental composition of melanin granules and other components of the hair shaft was determined by multi-isotope imaging mass spectrometry, a method with unique advantages for the visualization and quantification of stable isotopes and the elemental composition in study of the fine structure of biologic samples. We mapped and quantified the chemical composition of hair cross-sections using secondary ions generated from naturally occurring 16O, 12C14N, 32S, and 34S with a maximum lateral resolution of 35 nm. Based on these elemental maps of unprecedented resolution we obtained simultaneously the chemical fingerprints and the structural features, such as cuticle, melanin granules, the macro fibrils of the cortex, and small sulfur-rich domains in the medulla, in the hair cross-section. We found an intriguing distribution of 16O, 12C14N, and 32S in melanin granules that we interpret as a highly anisotropic pattern of oxidation.

Structure and function of human stratum corneum under deformation.

BACKGROUND: The stratum corneum (SC) has an important barrier function. The effect of a mechanical stress applied to the SC is controversial on this important physiological parameter. OBJECTIVES AND METHODS: To assess both in vitro and in vivo the structure and function of human SC submitted to controlled strains, we measured the transepidermal water loss (TEWL), in vivo, on human skin submitted to controlled strains ranging from 0 to 20% extension imposed by a Densi-score device. We also looked at the structure of the SC by means of X-ray diffraction and transmission electron microscopy. RESULTS: Transmission electron microscopy and X-ray diffraction analysis were performed on harvested and stretched human SC. TEWL was not significantly influenced by the relative deformation applied to the skin. At high strain (60%) imposed in vitro to the SC, lipid bilayers and corneosomes were detached from corneocytes. Only rare corneosomes showed internal disruption. X-ray analysis did not reveal modifications in the supramolecular organization of intercellular lipids while stretching the SC. CONCLUSION: Submitting human SC to an extension force up to 20% elongation does not significantly alter the barrier function.