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Foreign molecules in biomembranes : Molecular effects on intact stratum corneum and model lipid systems

Pham, Quoc Dat LU (2016)
Abstract (Swedish)
The skin is our largest organ and its main function is to protect us from uptake of foreign chemicals and from desiccation. The barrier function of the skin is mainly assured by its outermost layer, the stratum corneum (SC). When one wants to deliver a compound into or through the skin, for example in (trans)dermal drug delivery and cosmetics, one generally needs to make the skin more permeable. Therefore, it is desirable to control the skin barrier function. The purpose of this thesis is to deepen the understanding of the mechanisms that determine the skin permeability at a molecular level. The focus is laid on the molecular mobility and fluidity of components in SC, which play crucial roles in the barrier property. One major goal was to... (More)
The skin is our largest organ and its main function is to protect us from uptake of foreign chemicals and from desiccation. The barrier function of the skin is mainly assured by its outermost layer, the stratum corneum (SC). When one wants to deliver a compound into or through the skin, for example in (trans)dermal drug delivery and cosmetics, one generally needs to make the skin more permeable. Therefore, it is desirable to control the skin barrier function. The purpose of this thesis is to deepen the understanding of the mechanisms that determine the skin permeability at a molecular level. The focus is laid on the molecular mobility and fluidity of components in SC, which play crucial roles in the barrier property. One major goal was to characterize the fluid SC fractions and how they vary with different conditions, for example, hydration, temperature, addition of moisturisers and penetration enhancers, solvents and in diseased skin, for example, psoriasis. The molecular information can be related to other macroscopic properties of the skin, for example, water-holding capacity, elasticity, softness, dryness, and barrier function. The findings of this research can be applied in topical formulations for drug delivery and skin care products as well as for treatment of diseased skin. These results were achieved by performing experiments on intact SC, extracted corneocyte and model lipid systems and by combining different complementary techniques like NMR (nuclear magnetic resonance), scattering, calorimetry, sorption microbalance and diffusion-cell systems. (Less)
Abstract
This thesis mainly explores how the molecular mobility of lipid and protein components in the outermost layer of the skin, the stratum corneum (SC), varies with different conditions and upon adding foreign compounds. These studies require methods that makes it possible to detect and characterize the minor amount of fluid components in the highly ordered solid SC sample with resolved molecular information. 13C polarization transfer solid-state nuclear magnetic resonance (PT ssNMR) is well suited for this task, and was employed as the main method through this thesis. The aims of this thesis were achieved by studies on well-controlled systems of intact SC, extracted corneocyte, and model lipid systems, and by combining PT ssNMR with different... (More)
This thesis mainly explores how the molecular mobility of lipid and protein components in the outermost layer of the skin, the stratum corneum (SC), varies with different conditions and upon adding foreign compounds. These studies require methods that makes it possible to detect and characterize the minor amount of fluid components in the highly ordered solid SC sample with resolved molecular information. 13C polarization transfer solid-state nuclear magnetic resonance (PT ssNMR) is well suited for this task, and was employed as the main method through this thesis. The aims of this thesis were achieved by studies on well-controlled systems of intact SC, extracted corneocyte, and model lipid systems, and by combining PT ssNMR with different complementary biophysical techniques.
A general conclusion from the presented studies of different foreign compounds is that apolar compounds mainly affect SC lipids, while more polar compounds affect both SC lipid and protein components. The effects strongly depend on the identity of the additive, and on the hydration conditions, and they vary with concentrations and temperatures. One interesting finding is the essential role of water in the mobility of keratin filaments. Apart from the effects on SC components, one can also simultaneously characterize the molecular mobility of the additves that are incorporated in the complex SC matrix by using PT ssNMR.
We also demonstrate a clear correlation between the molecular mobility in SC lipids and proteins and the skin permeability upon additives, which forwards the understanding of the skin macroscopic barrier function at a molecular level. The findings of this research can be applied in topical formulations for, e.g., drug delivery and skin care products. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor Lafleur, Michel, Université de Montréal, Canada
organization
publishing date
type
Thesis
publication status
published
subject
keywords
stratum corneum, lipid, keratin filament, protein, DMPC, penetration enhancer, osmolyte, solvent, monoterpene, fatty acid, hydration, molecular mobility, fluidity, permeability, PT ssNMR, diffusion cell
pages
202 pages
publisher
Division of Physical Chemistry, Faculty of Science, Lund University
defense location
Center for chemistry and chemical engineering, lecture hall B, Naturvetarvägen 14, Lund
defense date
2016-09-23 10:15
ISBN
978-91-7422-468-9
language
English
LU publication?
yes
id
da0c28dd-99c1-4a44-add4-5068781110f4
date added to LUP
2016-08-29 10:47:01
date last changed
2016-09-19 08:45:20
@misc{da0c28dd-99c1-4a44-add4-5068781110f4,
  abstract     = {This thesis mainly explores how the molecular mobility of lipid and protein components in the outermost layer of the skin, the stratum corneum (SC), varies with different conditions and upon adding foreign compounds. These studies require methods that makes it possible to detect and characterize the minor amount of fluid components in the highly ordered solid SC sample with resolved molecular information. 13C polarization transfer solid-state nuclear magnetic resonance (PT ssNMR) is well suited for this task, and was employed as the main method through this thesis. The aims of this thesis were achieved by studies on well-controlled systems of intact SC, extracted corneocyte, and model lipid systems, and by combining PT ssNMR with different complementary biophysical techniques.<br/>A general conclusion from the presented studies of different foreign compounds is that apolar compounds mainly affect SC lipids, while more polar compounds affect both SC lipid and protein components. The effects strongly depend on the identity of the additive, and on the hydration conditions, and they vary with concentrations and temperatures. One interesting finding is the essential role of water in the mobility of keratin filaments. Apart from the effects on SC components, one can also simultaneously characterize the molecular mobility of the additves that are incorporated in the complex SC matrix by using PT ssNMR.<br/>We also demonstrate a clear correlation between the molecular mobility in SC lipids and proteins and the skin permeability upon additives, which forwards the understanding of the skin macroscopic barrier function at a molecular level. The findings of this research can be applied in topical formulations for, e.g., drug delivery and skin care products.},
  author       = {Pham, Quoc Dat},
  isbn         = {978-91-7422-468-9 },
  keyword      = {stratum corneum,lipid,keratin filament,protein,DMPC,penetration enhancer,osmolyte,solvent,monoterpene,fatty acid,hydration,molecular mobility,fluidity,permeability,PT ssNMR,diffusion cell},
  language     = {eng},
  pages        = {202},
  publisher    = {ARRAY(0x9f2b7d0)},
  title        = {Foreign molecules in biomembranes : Molecular effects on intact stratum corneum and model lipid systems},
  year         = {2016},
}