Abstract
A correlative methodology for label-free chemical imaging of soft tissue has been developed, combining nonlinear optical spectroscopies and mass spectrometry to achieve sub-micron spatial resolution and critically improved drug detection sensitivity. The approach was applied to visualise the kinetics of drug reservoir formation within human skin following in vitro topical treatment with a commercial diclofenac gel. Non-destructive optical spectroscopic techniques, namely stimulated Raman scattering, second harmonic generation and two photon fluorescence microscopies, were used to provide chemical and structural contrast. The same tissue sections were subsequently analysed by secondary ion mass spectrometry, which offered higher sensitivity for diclofenac detection throughout the epidermis and dermis. A method was developed to combine the optical and mass spectrometric datasets using image registration techniques. The label-free, high-resolution visualisation of tissue structure coupled with sensitive chemical detection offers a powerful method for drug biodistribution studies in the skin that impact directly on topical pharmaceutical product development.
Original language | English |
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Pages (from-to) | 79-89 |
Number of pages | 11 |
Journal | Journal of Controlled Release |
Volume | 364 |
Early online date | 27 Oct 2023 |
DOIs | |
Publication status | Published - 1 Dec 2023 |
Bibliographical note
Funding Information:This work was funded by Haleon CH SARL. CR is currently a consultant for Haleon CH SARL but was employed at CRL at the time of this work.The authors are grateful to Alex Shard (NPL) and David Moore (Omero Consulting Ltd) for helpful discussions, and to Marcel Niehaus (formerly NPL) for the preparation of veal brain homogenate. This work was funded by Haleon CH SARL. The contributions of NAB and RHG were supported in part by the Food and Drug Administration (FDA) of the U.S. Department of Health and Human Services (HHS) as part of a financial assistance award (1-U01-FD006533). The contents of this article are those of the authors and do not necessarily represent the official views of, nor an endorsement by, FDA/HHS or the U.S. Government. Support by the Community for Analytical Measurement Science is also gratefully acknowledged for a 2020 CAMS Fellowship Award to Natalie Belsey funded by the Analytical Chemistry Trust Fund.
Funding Information:
This work was funded by Haleon CH SARL . The contributions of NAB and RHG were supported in part by the Food and Drug Administration (FDA) of the U.S. Department of Health and Human Services (HHS) as part of a financial assistance award ( 1-U01-FD006533 ). The contents of this article are those of the authors and do not necessarily represent the official views of, nor an endorsement by, FDA/HHS or the U.S. Government. Support by the Community for Analytical Measurement Science is also gratefully acknowledged for a 2020 CAMS Fellowship Award to Natalie Belsey funded by the Analytical Chemistry Trust Fund .
Publisher Copyright:
© 2023 The Authors
Keywords
- Topical drug delivery
- Diclofenac
- Skin biodistribution
- Stimulated Raman scattering microscopy
- Secondary ion mass spectrometry
- OrbiSIMS
- Multiphoton imaging
- Correlative imaging