Leiden University Scholarly Publications

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Boiten, W.A. (2020)

Lipids as therapeutic targets for barrier repair in skin diseases

Doctoral Thesis
The skin is our natural barrier and lipids are a key part of this barrier. In the outer skin layer, the stratum corneum (SC), lipids form a densely organized structure dependent on the composition of these lipids. Multiple skin diseases are characterized by alterations in SC lipid composition. These alterations are related to pathological barrier defects. This thesis describes the next steps towards a treatment modifying the lipid composition and thereby restoring this barrier. We developed a novel method to quantify a key SC lipid group called ceramides. This method was applied to compare SC regeneration of skin models to healthy volunteers. Regeneration in such an ex vivo skin model proved to be a potent model for formulation development. Ensuing, a clinical study was performed to determine the mechanistic effects of a formulation on barrier repair in healthy skin. The results warranted follow up analysis of the formulation in atopic dermatitis patients. This thesis also...Show more The skin is our natural barrier and lipids are a key part of this barrier. In the outer skin layer, the stratum corneum (SC), lipids form a densely organized structure dependent on the composition of these lipids. Multiple skin diseases are characterized by alterations in SC lipid composition. These alterations are related to pathological barrier defects. This thesis describes the next steps towards a treatment modifying the lipid composition and thereby restoring this barrier. We developed a novel method to quantify a key SC lipid group called ceramides. This method was applied to compare SC regeneration of skin models to healthy volunteers. Regeneration in such an ex vivo skin model proved to be a potent model for formulation development. Ensuing, a clinical study was performed to determine the mechanistic effects of a formulation on barrier repair in healthy skin. The results warranted follow up analysis of the formulation in atopic dermatitis patients. This thesis also describes a detailed analysis of the ceramide fraction that is covalently attached to the cells in the SC. It was shown that a selected group of ceramides becomes bound. Further analysis showed that this group of ceramides was also affected in atopic dermatitis patients SC. Show less
Stratum corneum
Ceramides
Lipids
Skin barrier repair
Formulation
Vernix caseosa
Liquid chromatography mass sepectrometry
Lipidomics
Atopic dermatitis
Cornified lipid envelope
All authors
Boiten, W.A.
Supervisor
Bouwstra, J.A.
Co-supervisor
Smeden, J. van
Committee
Irth, H.; IJzerman, A.P.; Vermeer, M.H.; Rissmann, R.; Jiskoot, W.; Nicolaou, A.
Qualification
Doctor (dr.)
Awarding Institution
Leiden Academic Centre for Drugs Research (LACDR), Faculty of Science, Leiden University
Date
2020-01-15
ISBN (print)
9789463239929

Funding

Sponsorship
This research was financially supported by Dutch Technology Foundation TTW (grant no. 12400).