Geol, A; Pendlington, R; Glavin, S; Chen, T; Belsey, N A (2024) Characterisation of Skin Penetration Pathways using Stimulated Raman Scattering Microscopy. European Journal of Pharmaceutics and Biopharmaceutics, 204. 114518

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Abstract

Background: Understanding the mechanisms governing the penetration of substances into the skin is crucial for the development of effective topical and transdermal drug delivery systems as well as skincare products. Currently, this understanding of the interplay between molecular properties and penetration pathways is lacking.

Objectives: This study aimed to explore the permeation pathways of six model permeants across human skin, focusing on substances with diverse logP values.

Methods: We employed Stimulated Raman Scattering (SRS) microscopy, a label-free optical imaging technique known for its ability to provide detailed mechanistic insights into chemical distribution with subcellular resolution. The distribution of six model permeants within the skin with diverse logP values ranging from 7.17 to -0.92 was visualized, categorizing them based on their lipophilicity. The differential uptake of permeants in lipid-rich and lipid-poor compartments was analysed using skin lipids signals as morphological markers.

Results: Our investigation assessed two primary pathways through which substances traverse the skin: the intercellular lipid matrix and the intracellular route via corneocyte cells. We observed that the partition behaviour was strongly influenced by the lipophilicity of the molecule, with lipophilic compounds showing greater affinity for intercellular matrix with increased lipophilicity. Conversely, hydrophilic molecules demonstrated a preference for corneocyte cells, with their affinity for this pathway increasing with increase in hydrophilicity.

Conclusions: To quantify the differential uptake of permeants in these pathways, partition factors were calculated, providing insights into the dynamics of skin permeation. Discrepancies between experimental partition factors and model-predicted values were noted, potentially due to formulation effects and inherent limitations of the model. This pioneering study represents the first application of SRS microscopy to elucidate permeation pathways and their quantification within human skin across a wide range of logP values. The findings contribute to our understanding of the mechanisms underlying topical delivery and offer implications for the development of safe and effective topical products.

Item Type:	Article
Keywords:	Stimulated Raman scattering microscopy; Topical drug delivery; Cutaneous absorption; Raman spectroscopy
Subjects:	Nanoscience > Surface and Nanoanalysis
Divisions:	Chemical & Biological Sciences
Identification number/DOI:	10.1016/j.ejpb.2024.114518
Last Modified:	27 Nov 2024 11:08
URI:	https://eprintspublications.npl.co.uk/id/eprint/10099