Leiden University Scholarly Publications

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Uche, L.E. (2021)

Lipid model membrane systems as a tool for unraveling the underlying factors for skin barrier dysfunction

Doctoral Thesis
Barrier function is the natural role of the skin. The lipid matrix present in the outermost layer of the skin, the stratum corneum is important for this function. Barrier impairment and altered lipid composition are observed in several inflammatory skin diseases including atopic dermatitis and psoriasis. However, the relationship between the lipid properties and barrier function is not comprehended.
In this project, a lipid model was prepared from synthetic lipids that closely resemble the stratum corneum lipid composition and organization. Subsequently, diseased skin models were developed to mimic various abnormalities in lipid composition observed in atopic dermatitis patients’ skin. Biophysical methods were used to monitor the changes in lipid organization in these models. Diffusion studies and trans-epidermal water loss measurements were performed to monitor the barrier function. This allowed the determination of the changes in lipid properties that were most instrumental...Show moreBarrier function is the natural role of the skin. The lipid matrix present in the outermost layer of the skin, the stratum corneum is important for this function. Barrier impairment and altered lipid composition are observed in several inflammatory skin diseases including atopic dermatitis and psoriasis. However, the relationship between the lipid properties and barrier function is not comprehended.
In this project, a lipid model was prepared from synthetic lipids that closely resemble the stratum corneum lipid composition and organization. Subsequently, diseased skin models were developed to mimic various abnormalities in lipid composition observed in atopic dermatitis patients’ skin. Biophysical methods were used to monitor the changes in lipid organization in these models. Diffusion studies and trans-epidermal water loss measurements were performed to monitor the barrier function. This allowed the determination of the changes in lipid properties that were most instrumental in reducing the lipid barrier.
This thesis further describes the use of simple skin lipid model membranes incorporating fewer components to provide a detailed insight into the relationship between lipid composition, lipid organization, and the skin barrier. The information gained in this project offers the opportunity to develop a new generation of formulations to treat these patients.Show less
Atopic dermatitis
Ceramide
Free fatty acids
Infrared spectroscopy
Intercellular lipid
Long periodicity phase
Permeability
Sphingolipids
Stratum corneum
X-ray scattering
All authors
Uche, L.E.
Supervisor
Bouwstra, J.A.
Co-supervisor
Beddoes, C.M.
Committee
Irth, H.; Kuiper, J.; Rissmann, R.; Kros, A.; Lawrence, J.; Lopez Serrano, O.
Qualification
Doctor (dr.)
Awarding Institution
Leiden Academic Centre for Drug Research (LADCR), Faculty of Science, Leiden University
Date
2021-12-14
ISBN (print)
9789464215489