Zarmpi, P; Tsikritsis, D; Vorng, J-L; Belsey, N A; Bunge, A L; Woodman, T J; Delgado-Charro, M B; Guy, R H (2024) Evaluation of chemical disposition in skin by stimulated Raman scattering microscopy. Journal of Controlled Release, 368. pp. 768-807.

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Abstract

Tracking drug disposition in the skin in a non-destructive and semi-quantitative fashion is a relevant objective for the assessment of local (dermal) bioavailability. Confocal Raman spectroscopy has been shown potentially useful in this regard and, importantly, recent advances have enabled the presence of applied chemicals in the viable epidermis below the stratum corneum (SC) to be determined without ambiguity, due to the challenges of background signals from endogenous species and noise, and from signal attenuation due to absorption and scattering. This study aimed to confirm these findings using a different vibrational spectroscopy approach - specifically, stimulated Raman scattering (SRS) microscopy – and the more conventional in vitro skin penetration test (IVPT). SRS is a nonlinear optical imaging technique which enables more precise location of the skin surface and enhanced skin depth resolution relative to confocal Raman microscopy. The method can also probe larger areas of the sample under investigation and identify the localization of the permeating chemical in specific structural components of the skin. Here, SRS was shown capable of tracking the uptake and distribution of 4-cyanophenol (CP), the same model compound used in the recent confocal Raman investigation, at depths beyond the SC following skin treatment with different vehicles and for different times. The SRS results correlated well with those from the confocal Raman experiments, and both were consistent with independent IVPT measurements. Acquired images clearly delineated CP preference for the intercellular lipid layers of the SC relative to the corneocytes. The stage is now set to apply these and other correlative techniques to examine commercial drug products.

Item Type:	Article
Keywords:	Raman spectroscopy; Stimulated Raman scattering microscopy; In vitro permeation test; Cutaneous pharmacokinetics; Drug disposition in skin
Subjects:	Nanoscience > Surface and Nanoanalysis
Divisions:	Chemical & Biological Sciences
Identification number/DOI:	10.1016/j.jconrel.2024.02.011
Last Modified:	25 Sep 2024 13:29
URI:	https://eprintspublications.npl.co.uk/id/eprint/10058