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Analytical and Bioanalytical Chemistry

, Volume 410, Issue 11, pp 2815–2828 | Cite as

MALDI imaging facilitates new topical drug development process by determining quantitative skin distribution profiles

  • David Bonnel
  • Raphaël Legouffe
  • André H. Eriksson
  • Rasmus W. Mortensen
  • Fabien Pamelard
  • Jonathan Stauber
  • Kim T. Nielsen
Research Paper

Abstract

Generation of skin distribution profiles and reliable determination of drug molecule concentration in the target region are crucial during the development process of topical products for treatment of skin diseases like psoriasis and atopic dermatitis. Imaging techniques like mass spectrometric imaging (MSI) offer sufficient spatial resolution to generate meaningful distribution profiles of a drug molecule across a skin section. In this study, we use matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to generate quantitative skin distribution profiles based on tissue extinction coefficient (TEC) determinations of four different molecules in cross sections of human skin explants after topical administration. The four drug molecules: roflumilast, tofacitinib, ruxolitinib, and LEO 29102 have different physicochemical properties. In addition, tofacitinib was administrated in two different formulations. The study reveals that with MALDI-MSI, we were able to observe differences in penetration profiles for both the four drug molecules and the two formulations and thereby demonstrate its applicability as a screening tool when developing a topical drug product. Furthermore, the study reveals that the sensitivity of the MALDI-MSI techniques appears to be inversely correlated to the drug molecules’ ability to bind to the surrounding tissues, which can be estimated by their Log D values.

Graphical abstract

Keywords

Mass spectrometry imaging MALDI-MSI Human skin Quantification Drug distribution Skin penetration 

Notes

Acknowledgements

We acknowledge Tina Leonhardt Hjort for the execution of the drug penetration study, Liselotte Saustrup Kirk for the UHPLC-MS/MS analysis of the tissue samples, and Lotte Koue for the help with the production of the formulations. We also acknowledge Torsten Kåre Askland, Edma Edge Fontaine, and Mathieu Gaudin for helping with the proofreading.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

The study involved anonymized human skin samples from abdominoplasty surgery acquired from Biopredic International, France, upon written informed consent from the donor.

Ethical approval

According to the Danish Committee Act section 14.3, anonymous human biological material used in health research projects shall not seek ethical approval as long as the collected human biological material has been collected lawfully in the country of origin which is the case. The supplier of the human biological material holds a permit granted by the French Ministry of Higher Education and Research for the acquisition, transformation, sales, and export of human biological material to be used in research, and is furthermore in compliance with the French law CSP1245-2.

Supplementary material

216_2018_964_MOESM1_ESM.pdf (220 kb)
ESM 1 (PDF 220 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • David Bonnel
    • 1
  • Raphaël Legouffe
    • 1
  • André H. Eriksson
    • 3
  • Rasmus W. Mortensen
    • 3
  • Fabien Pamelard
    • 1
  • Jonathan Stauber
    • 1
    • 2
  • Kim T. Nielsen
    • 3
  1. 1.ImaBiotech SAS, Parc EurasantéLoosFrance
  2. 2.ImaBiotech CorpBillericaUSA
  3. 3.LEO Pharma A/SBallerupDenmark

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