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... 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
The research described in this thesis shows that hypercholesterolemia, a well-established risk factor for atherosclerosis, can impact skin lipid pool and barrier function already at young age. In... Show moreThe research described in this thesis shows that hypercholesterolemia, a well-established risk factor for atherosclerosis, can impact skin lipid pool and barrier function already at young age. In the field of atherosclerosis, we showed that the small peptide Lyp-1 can be used as a targeting molecule in liposomal formulations to deliver liver X receptor agonist to plaque resident foam cells/lipid-rich macrophages. Elucidation of the mechanisms underlying the intercommunication between plasma lipids and skin lipids may also bring valuable opportunities to prevent and treat dermatological pathologies in dyslipidemic patients; perhaps in combination with anti-atherogenic therapies. Thus, by deepening our knowledge we may improve our advice to the patients and ultimately improve their quality of life. Show less
The stratum corneum is the outermost layer of the skin, and acts as the primary barrier against penetration of pathogens, allergens and other exogenous substances into the lower layers of the skin.... Show moreThe stratum corneum is the outermost layer of the skin, and acts as the primary barrier against penetration of pathogens, allergens and other exogenous substances into the lower layers of the skin. Crucial for a proper barrier function are the lipids in the stratum corneum, mainly consisting of ceramides, free fatty acids, and cholesterol. These lipids are highly ordered stacked layers. In atopic eczema the skin barrier is impaired, but the exact role of the lipids is still uncertain. This thesis describes the importance of a proper composition and ordering of the stratum corneum lipids and their role in eczematous patients (atopic eczema and Netherton disease). The results demonstrate that patients suffering from a impaired skin barrier also show different lipid profile. In particular the carbon chain length of the lipids is notably reduced in these eczematous patients. Consequently, the stratum corneum lipids show a less ordered lipid arangement. This is the first time that a strong correlation is observed between the lipid composition, the lipid organization, and the skin barrier function. These studies therefore provide new targets for possible drug therapy of eczematous patients. Show less
