JCJC SVSE 5 - JCJC - SVSE 5 - Physique, chimie du vivant et innovations biotechnologiques

Raman qualitative and quantitative descriptors of dry skin diseases : Cutaneous hydration Anomalies - a Raman Evaluation – CARE

CARE : Cutaneous hydration Anomalies : a Raman Evaluation

Raman qualitative and quantitative descriptors of dry skin diseases : relation between hydration rates and the conformational and organisational state of lipids and the secondary structure of proteins in the stratum corneum

Understanding the molecular aspects of «dry skin” diseases

The “dry skin” holds a dominating place in dermatology and in cosmetic applications. Skin dryness will be for the former, a discomfort due to the ageing, resulting from climatic effects or sun exposures, whereas for the latter the clinical sign of an ill-defined pathogenic dysfunction, for instance lack of barrier function. It can be clinically defined as a rough and scaly skin which generates feelings of discomfort, tightness and pruritus. In addition to that, “dry skin” could have real social consequences and may affect severely the quality of life by the unaesthetic aspect of the skin and the skin discomfort (pruritis, pain related to cracks).<br />Several biophysical techniques have been developed during the last decade in order to improve skin description and knowledge, driven by medical, pharmaceutical, and cosmetic researches. Nevertheless, dry skin has never been really explored, characterized and defined as a specific outcome of a particular physiological or pathological phenomenon in a reliable manner. The aim of the project is to develop models of dry skin on which the direct or indirect measurements of the hydration level. It would be of a great help in dermatological departments for clinical diagnosis and therapy, and in pharmaceutical and cosmetic industries for safety and efficacy testing of topically applied product. In addition to that, the access to this information could provide new control elements for regulation authorities (“Agence Narionale de Sécurité du Médicament” ANSM (formerly AFSSAPS), European Medicines Agency (EMA)…) and Cosmetic regulation authorities.

In order to study the different molecular aspects of skin hydration, the use of non-invasive methods is required. Vibrational spectroscopies (Raman and infrared) are non-destructive, non-invasive and informative techniques that present high efficiency for in vitro and ex vivo investigations. This could assess subtle differences to supplement traditional studies.
The use of Raman spectroscopy enables to transfer the spectral descriptors from ex vivo to in vivo.

The first ex vivo results enabled to highlight the important role of water structure in the hydration process. Different types of water were identified: Tightly bound (with 4 hydrogen bonds with the stratum corneum components), partially bound (with 1, 2 or 3 hydrogen bonds with the stratum corneum) and unbound water.
Among these types of water, partially bound water seems to have direct influence on the lipids conformational order and organisation as well as on the secondary structure and the folding of proteins.
On the other hand, based on the pre-established spectral descriptors, we have proposed a new approach to evaluate the action of different moisturizers.

The next step will be the association between skin hydration and skin aging. In vitro and ax vivo analyses are scheduled in order to highlight new descriptors for skin aging.
The final aim of the project is the transfer of the know-how into in vivo investigations. The pre-defined spectral descriptors will be validated on a panel of volunteers.

1. VYUMVUHORE R. et al.. Analyst, 2013, Vol. 138. Pages 4103-4111
2. TFAYLI A. et al. Analyst, 2013, Vol. 138, Issue 21, pages 6582 – 6588
3. TFAYLI A. et al. Exp. Derm. 2014, 23, 441-443.
4. VYUMVUHORE R. et al. Skin Res. Technol. 2014 Aug;20(3):282-92.

Congres:
1. TFAYLI A., FARHANE Z., BONNIER F., VYUMVUHORE R., LIBONG D., BYRNE H.J., Baillet-Guffroy A. « Structure and organization of cutaneous lipids in a reconstructed skin model: Raman microspectroscopy and HPLC analysis. ». European Conference on the Spectroscopy of Biological Molecules (ECSBM), August 2013, Oxford, UK
2. QUATELA A.,TFAYLI A., PIOT O., MANFAIT M., Baillet-Guffroy A. « Raman spectroscopy: a tool for in-depth molecular profiling in skin ». International conference of Raman spectroscopy (ICORS), August 2014,Jena, Germany

Skin dryness is the clinical sign of an ill-defined pathogenic dysfunction related to a lack in barrier function. It can be clinically defined as a rough and scaly skin which generates feelings of discomfort, tightness and pruritus. The occurrence of dry skin is dependant on many extrinsic factors including climate, environment and exposure to chemicals or medications. There is also a variety of intrinsic factors that can contribute to the condition, such as genetics, diseases, hormone imbalances and ageing.
The concern of “dry skin” and skin hydration holds a dominating place in dermatology and skin research, mainly targeting the improvement of the stratum corneum SC (the outermost layer of the skin) barrier function.
Despite the advancement in the understanding of the structure, composition, formation and function of the stratum corneum (SC) over the last few decades, dry skin remains the most common of human skin disorders.
Several biophysical techniques have been developed in order to improve skin description and knowledge, driven by medical, pharmaceutical, and cosmetic researches. Nevertheless, dry skin has never really been explored, characterized and defined as a specific outcome of a particular physiological or pathological phenomenon in a reliable manner.
Infrared and Raman spectroscopies are non-destructive, non-invasive and informative techniques that present high efficiency for in vitro and ex vivo investigations. No sample preparation is required. Moreover, the use of Raman for in vivo analysis of the skin has been widely recognised. It enables, not only to monitor water gradients in tissue, but also to survey structural, conformational or organizational changes in SC lipids and the secondary structure of proteins.
The aim of this work will be to establish a clear, reproducible and reliable relation between the hydration rate and the changes in the conformational and organizational descriptors of lipids or the secondary structure of proteins in the stratum corneum. This information will be first validated in vitro and ex vivo and then transferred for in vivo analysis.
One of the main advantages of confocal Raman microspectroscopy is the micrometric spatial localization at different depths under the skin surface. Unfortunately, the air / sample interface perturbs the confocal properties due to the light refraction leading to very large deformation in the resolution and to a misestimation of the depth value. Such errors may have heavy consequences on the physiological interpretation of the molecular data. One of the aims of this work will be to correct the depth and the resolution values by using physical and optical theoretical models.
The actual project proposes a transversal vision from fundamental research work (spectral descriptors and correct spatial information) to applied and clinical aspects (effect of dry skin diseases, skin aging and effect of moisturizers). It can be of great interest for the characterization of dry skin processes, and therefore for the development of new therapies for the prevention and correction of dermatological disorders related with low water content.
CARE is the evolution of a previous unfunded JCJC2011 proposition (SHyRA). It takes into account the remarks of reviewers and SVSE5 committee.

Project coordination

Ali Tfayli (Université Paris-Sud, Groupe de Chimie Analytique de Paris-Sud, ) – ali.tfayli@u-psud.fr

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

PSUD, GCAPS Université Paris-Sud, Groupe de Chimie Analytique de Paris-Sud,

Help of the ANR 240,240 euros
Beginning and duration of the scientific project: January 2013 - 36 Months

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