Ali Tfayli

• PhD
• Professor (Full) at University of Paris-Saclay

Skin health relies heavily on a well-maintained cutaneous barrier. While the detrimental effects of UV radiation on the epidermis are established, the impact of blue light, a significant component of sunlight and artificial sources, is less clear. This study aims to explore blue light's influence on the reconstructed human epidermis (RHE) using two...

Atopic dermatitis (AD) is associated with chronic inflammation and an altered skin barrier. Lipids of the stratum corneum of AD patients are known to differ substantially in composition from those of healthy subjects. A reconstructed human epidermis (RHE) model has been developed in vitro in order to mimic the characteristics of AD. In this study,...

The skin surface lipids (SSLs) film, composed of sebum and keratinocyte membrane lipids, is crucial to the barrier function of the stratum corneum (SC). The first part of this study investigated the impact of solar radiation on the SC based on a novel hydration and dehydration approach using Raman spectroscopy. The SSLs were found to absorb solar l...

Blue light therapy is increasingly used to treat various skin conditions like acne, psoriasis, and neonatal hyperbilirubinemia. Yet, excessive blue light exposure can also negatively impact human health by disrupting circadian rhythms, generating free radicals, and damaging skin barrier function. Quantifying personal blue light exposure is therefor...

Background Reconstructed epidermis models, obtained from 3D keratinocytes culture, have gained significant prominence as prototypes for safety and efficacy testing in skin research. To effectively evaluate these models, it is essential to perform molecular and functional characterization. The skin's barrier function is one of the essential aspects...

This study used Raman spectroscopy to develop a new approach to evaluate the effects of solar radiation on the stratum corneum (SC). The method measures the SC's hydration and dehydration kinetics by calculating the vOH/vCH ratio to monitor the relative water content during the drying process. The study also investigated the role of skin surface li...

Triglycerides (TGs) are one of the main components of the glycerolipid family. Their main task in cells is to store excess fatty acids. TG energy storage is mainly concentrated in adipocytes. TGs and free fatty acids constitute the majority (57.5%) of the skin surface lipids (SSLs). TGs are essential for the formation of the skin water barrier. Thi...

Atherosclerosis – a cardiovascular disease and the primary cause of morbidity and mortality in industrialized countries – is linked to the existence of atherosclerotic plaques characterized by cholesterol-laden macrophages called foam cells. In these cells, cholesterol esters associated with triglycerides form lipid droplets (LD). The only way to r...

Skin surface lipid (SSL) film is a mixture of sebum and epidermal lipids protecting skin from environment such as solar radiation. SSLs are a suitable target and scavenger for all reactive oxygen species (ROS) generated in the skin. In the skin surface lipids, vitamin E has been identified as one of the main antioxidants, which can capture reactive...

The study of human skin represents an important area of research and development in dermatology, toxicology, pharmacology and cosmetology, in order to assess the effects of exogenous agents, their interaction, their absorption mechanism, and/or their toxicity towards the different cutaneous structures. The processes can be parameterised by mathemat...

In the present work, two photosensitizing drugs, Temoporfin and Verteporfin have been studied. Both have regular approval in Europe, Temoporfin for the treatment of head and neck cancers and Verteporfin for the treatment of age-related macular degeneration (AMD). The treatment modality, known as “Photodynamic Therapy” (PDT), involves drug activatio...

Lipid peroxidation (LPO) is an oxidative deterioration when oxidants such as reactive oxygen species attack lipids that contain double bonds especially polyunsaturated fatty acids (PUFAs). The mechanism of lipid peroxidation is composed of three steps: initiation, propagation and termination. It can result from several reaction pathways : (1) auto‐...

The epidermal protective functions are closely associated with skin hydration homeostasis. The understanding of different states of water binding is a rising concept in assessing topically applied formulations and their interaction within the stratum corneum (SC). In addition to global water content, primary bound water, partially bound water, and...

The study of human skin represents an important area of research and development in dermatology, toxicology, pharmacology and cosmetology, in order to assess the effects of exogenous agents, their interaction, their absorption mechanism, and/or their toxicity towards the different cutaneous structures. The processes can be parameterised by mathemat...

Confocal Raman microscopy (CRM) has become a versatile technique that can be applied routinely to monitor skin penetration of active molecules. In the present study, CRM coupled to multivariate analysis (namely PLSR—partial least squares regression) is used for the quantitative measurement of an active ingredient (AI) applied to isolated (ex vivo)...

The presence of a new ceramide subclass, the 1-O-acyl omega-linoleoyloxy ceramides [1-O-E (EO) Cer], has been previously highlighted in reconstructed human epidermis (RHE). These ceramides are double esterified on two positions. The first is the 1-O position of the sphingoid base moiety with a long to very long chain of acyl residues (1-O-E), and t...

The stratum corneum (SC) plays an important role in skin barrier function. It acts as a protective barrier against water loss, eliminates foreign substances and micro-organisms and acts against harmful effects of UVR. our aim was to study the impact of suberythemal doses of UVA and UVB exposure on the molecular structure, organization and barrier f...

Surface Enhanced Raman Scattering (SERS) spectroscopy is a rapid and innovative analysis technique involving metallic nanoparticles (NPs). The interaction between NPs and norepinephrine gives an exaltation of the Raman signal under certain experimental conditions. The control of the signal exaltation, crucial for sensitive analyses, remains one of...

Surface-enhanced Raman spectroscopy (SERS) is a powerful analytical technique capable of increasing the Raman signal of an analyte using specific nanostructures. The close contact between those nanostructures, usually a suspension of nanoparticles, and the molecule of interest produces an important exaltation of the intensity of the Raman signal. E...

There exist different methods for the determination of sun protection factor (SPF) values for sunscreens. We aimed to develop a new in vitro method using EBT3 Gafchromic® film as a substrate. The colour of EBT3 Gafchromic® film changes when exposed to UV light. Films were covered by sunscreen preparations of different SPF values ranging from 0 to 5...

Reconstructed human epidermis models are used as epidermis alternatives in skin research studies. It is necessary to provide molecular and functional characterization in order to assess these models. Our aim is to establish a link between the barrier function and the structure and composition of the stratum corneum using several complementary techn...

Skin aging is a multifactorial phenomenon that involves alterations at the molecular, cellular, and tissue levels. Our aim was to carry out a multiparametric biophysical and Raman characterization of skin barrier between individuals of different age groups (<24 and > 70 years old). Our results showed a significant decrease of lipids to proteins rat...

Atherosclerosis is an inflammatory disease of the arterial wall caused by the formation of an atheroma plaque in the vessel wall. The uptake of modified LDL lipoproteins by sub-endothelial macrophages induces the latter's transformation into foam cells, which is the key step of atheroma plaque formation. The modifications of neutral lipids caused b...

From the basal layer until the stratum corneum, lipid and protein biomarkers associated with morphological changes denote keratinocyte differentiation and characterize each epidermis layer. Herein, we followed keratinocyte differentiation in the early stages using HaCaT cells over a period of two weeks by two complementary analytical techniques: Ra...

The stratum corneum (SC) is key in the maintenance of the biomechanical barrier and hydration of skin. Our previous investigations showed beneficial effects of a combination of emollients on water capture and retention and protein and lipid organization, all of which are linked to dryness and dry skin damage. Here, we show how a formulation contain...

Confocal Raman Mapping (CRM) is a powerful, label free, non‐destructive tool, enabling molecular characterisation of human skin with applications in the dermo‐cosmetic field. Coupling CRM to multivariate analysis can be used to monitor the penetration and permeation of Active Cosmetic Ingredients (ACI) after topical application. It is presently ill...

The importance of the hydrolipidic film of skin has been well documented, however, few data are available in cases of very old age. Our aim was to characterize the difference in skin surface lipid (SSL) composition between individuals of different age groups. Data were collected from the forehead of 22 young volunteers (18-24 years old) and 18 seni...

Antineoplastic agents are, for most of them, highly toxic drugs prepared at hospital following individualized prescription. To protect patients and healthcare workers, it is important to develop analytical tools able to identify and quantify such drugs on a wide concentration range. In this context, surface enhanced Raman spectroscopy (SERS) has be...

Stratum corneum lipids are responsible for the skin's barrier function. They are the final product of epidermis lipid biosynthesis. During this process, lipids evolve from simple to complex structures in three main levels respectively (stratum basal level, stratum granulosum level, and stratum corneum level). Our aim was to simultaneously analyze a...

Background: Hyperpigmentation disorders are considered signs of skin aging and are aesthetically unpleasant. Most active ingredients used against hyperpigmentation disorders predominantly target tyrosinase activity. Objectives: To study the effect of two Origanum essential oils on the melanogenic activity of B16-F1 murine melanocytes. The main c...

Background: Skin depigmentation is increasingly oriented toward plant extracts because of harmfulness of depigmenting active ingredients used in cosmetics and dermatology. Reconstructed human pigmented epidermis (RHPE) is the closest in vitro model to human skin and offers the possibility to test the global depigmenting effect of a plant extract....

Anticancer drugs are prescribed and administrated to an increasing number of patients on a daily basis. As a consequence, a number of concerns have been raised about the patient health and safety in the case that the drugs administered are not at the required concentration or even worse not the correct ones. Quality control of therapeutic solutions...

Objective In our study, we aim to explore the ability of four essential oils (EO) of Lebanese plants to inhibit the tyrosinase activity and to correlate their efficiency level to their phytochemical compositions. Methods The EO have been extracted by hydrodistillation using a Clevenger apparatus and have been studied by GC‐MS analysis. Active comp...

Objective: Although xerosis is a common skin disorder among the population, there is no in vivo global study focusing on xerotic skin. Hence, the objective of this study was to characterize xerotic skin from the surface to the molecular scale with in vivo and non-invasive approaches. Methods: For this purpose, 15 healthy volunteers with normal s...

After life in utero and birth, the skin is submitted to an important process of adaptation to a relatively dry gaseous environment. Skin surface lipids (SSLs) contribute actively to the protection of the skin barrier. Within this context, our objective was to study the evolution of each lipid compound during the postnatal period. SSLs were collecte...

This study was conducted to evaluate the ability of Raman spectroscopy (RS) to control antineoplastic preparations used for chemotherapy in order to ensure its physical and chemical qualities. Three taxane drugs: cabazitaxel (CBX), docetaxel (DCX) and paclitaxel (PCX) at therapeutic concentration ranges were analyzed using a handheld spectrometer a...

Fourier Transform Infrared (FTIR) microspectroscopy was used to highlight the interactions between two photosensitisers (PS) of different geometries, TPPmOH4 and a glycoconjugated analogous, TPPDegMan, and lipid bilayers modelling retinoblastoma cell membranes. Retinoblastoma is a rare disease occurring in young infants, for whom conservative treat...

An important aspect of the biomechanical behavior of the stratum corneum (SC) is the drying stresses that develop with water loss. These stresses act as a driving force for damage in the form of chapping and cracking. Betasitosterol is a plant sterol with a structure similar to cholesterol, a key component in the intercellular lipids of the outermo...

The present work deals with original bi-compartmental lipid Janus nanoparticles (JNP) which are characterized by the presence of an oily compartment associated with an aqueous compartment delimited by a phospholipid-based bilayer. The size of JNP varies between 150 and 300 nm. As JNP are promising candidates for cutaneous application, the purpose o...

The use of monoclonal antibodies (mAbs) constitutes one of the most important strategies to treat patients suffering from cancers such as hematological malignancies and solid tumors. These antibodies are prescribed by the physician and prepared by hospital pharmacists. An analytical control enables the quality of the preparations to be ensured. The...

Skin aging is one of the most common dermatologic concerns in modern society. Because of its social impact, skin aging is particularly important and an increasing part of the population looks for new creams and procedures that can improve the appearance of the skin. Beyond these aspects, clinical manifestations of skin aging like xerosis, wrinkles...

Introduction Le contrôle analytique des chimiothérapies permet d’assurer la qualité physico-chimique des préparations. La spectroscopie vibrationnelle Raman (SR) est une technique rapide, non destructive et non invasive largement utilisée dans l’industrie pharmaceutique. L’objectif de cette étude a été de montrer la faisabilité de la SR pour la dis...

Topically applied Active Cosmetic Ingredients (ACI) or Active Pharmaceutical Ingredients (API) efficacy is directly related to their efficiency of penetration in the skin. In vitro Reconstructed Human Epidermis (RHE) surrogate models offer in vivo like skin samples for transdermal studies. Using Delipidol®, an ACI currently used in the cosmetics in...

The aim of this study was to assess the ability of Raman spectroscopy to discriminate and quantify five antineoplastic drugs in an aqueous matrix at low concentrations before patient administration. Five antineoplastic drugs were studied at therapeutic concentrations in aqueous 0.9% sodium chloride: 5-fluorouracil (5FU), gemcitabine (GEM), cyclopho...

Monoclonal antibodies constitute one of the most important strategies to treat patients suffering from cancers such as hematological malignancies and solid tumors. In order to guarantee the quality of those preparations prepared at hospital, quality control has to be developed. The aim of this study was to explore a noninvasive, nondestructive, and...

Raman spectroscopy is a rapid, non-destructive and non-invasive method that is a promising tool for real-time analytical control of drug concentrations. This study evaluated a handheld Raman device to discriminate and quantify two isomeric drugs used to treat cancer. Doxorubicin (DOXO) and epirubicin (EPIR) samples were analyzed at therapeutic conc...

Background: In vivo Raman spectroscopy is a powerful tool for real-time analysis and in situ evaluation of tissues such as the skin. The efficiency of this technique has been widely demonstrated as a label-free method for in vivo evaluation of the skin. The aim of this study is to gather information about inter- and intra-individual variations in...

Plasticized PVC is widely used to make medical devices such as tubing, perfusion bags and blood bags. By using confocal Raman microscopy on a PVC sheet plasticized with around 40% of di-(2-ethylhexyl)phthalate (DEHP), we propose a simple and sensitive approach to studying and understanding the diffusion of plasticizers from polymers into the surrou...

Stratum Corneum (SC) is the most superficial layer of the epidermis. It plays the main barrier role against water loss and the aggression of external chemical and biological substances. Thermal treatment in warm purified water followed by trypsin incubation of excised human skin is a well-established in vitro method for SC removal. Different protoc...

Dermatologists need to combine different clinically relevant characteristics for a better understanding of skin health. These characteristics are usually measured by different techniques, and some of them are highly time consuming. Therefore, a predicting model based on Raman spectroscopy and partial least square (PLS) regression was developed as a...

The use of animals for scientific research is increasingly restricted by legislation, increasing the demand for human skin models. These constructs present comparable bulk lipid content to human skin. However, their permeability is significantly higher, limiting their applicability as models of barrier function, although the molecular origins of th...

Proper hydration of the stratum corneum (SC) is important for maintaining skin's vital functions. Water loss causes development of drying stresses, which can be perceived as ‘tightness’, and plays an important role in dry skin damage processes. However, molecular structure modifications arising from water loss and the subsequent development of stre...

Skin dryness is an omnipresent symptom in various types of skin disorders. Thereby, a large panel of skin care products is developed for therapeutic purposes. However, there is still a lack of non-invasive methods to determine the mechanisms of action of moisturizers at the molecular level. In the present study, confocal Raman spectroscopy coupled...

The stratum corneum is the outermost layer of the skin; its barrier function is highly dependent on the composition and the structure as well as the organization of lipids in its extracellular matrix. Ceramides, free fatty acids and cholesterol represent the major lipid classes present in this matrix. They play an important role in maintaining the...

The mechanical properties of the Stratum Corneum (SC) have been studied by different authors at the macroscopic level, but the modification of its ultra structure during mechanical extension remains unknown. Moreover, little is described about the effect of the mechanical stress on SC barrier function. In this study, we have examined the SC structu...

Curing is generally required to stabilize film coating from aqueous polymer dispersion. This post-coating drying step is traditionally carried out in static conditions, requiring the transfer of solid dosage forms to an oven. But, curing operation performed directly inside the coating equipment stands for an attractive industrial application. Recen...

Raman spectroscopy coupled with K-means clustering analysis (KMCA) is employed to elucidate the biochemical structure of human skin tissue sections and the effects of tissue processing. Both hand and thigh sections of human cadavers were analyzed in their unprocessed and formalin-fixed, paraffin-processed (FFPP), and subsequently dewaxed forms. In...

Skin hydration plays an important role in the optimal physical properties and physiological functions of the skin. Despite the advancements in the last decade, dry skin remains the most common characteristic of human skin disorders. Thus, it is important to understand the effect of hydration on Stratum Corneum (SC) components. In this respect, our...

This document sets out the theoretical and practical fundamentals to guide users in the implementation of Raman spectroscopy in industry or the university-hospital sector. It describes the principle of this technique and currently available instruments. Since Raman spectrometers are used in a regulated context, the methodology of instrument qualifi...

The dissolution method is still widely used to determine curing end-points to ensure long-term stability of film coatings. Nevertheless, the process of curing has not yet been fully investigated. For the first time, joint techniques were used to elucidate the mechanisms of dynamic curing over time from ethylcellulose (Aquacoat)-based coated tablets...

The main function of the stratum corneum (SC) is for protection against external aggression. This is described as the barrier function. It mainly depends on the presence of a lipid matrix composed of ceramides, free fatty acids, cholesterol and its derivatives in the intercellular spaces. Previous studies have reported the application of Raman spec...

Skin surface lipids (SSLs), arising from both sebaceous glands and skin removal, form a complex lipid mixture composed of free fatty acids and neutral lipids. They are present in the hydrolipidic film and have a close relationship with the stratum corneum lipids. Thus, SSLs participate in the barrier function. One can expect a physiological adaptat...

Raman microspectroscopy has been shown to enable the identification of micro-particles inside sealed glass containers for pharmaceutical use without any sample preparation. Raman spectra were collected from unknown particles with a maximum size of 1mm, adsorbed on the inner surface of ampoules. The particles were clearly identified as primarily hem...

The outermost layer of the mammalian skin, the stratum corneum (SC), represents the main skin barrier. The SC lipids have a very exceptional composition, as the main lipid classes are ceramides (CER), long-chain fatty acids and cholesterol. Information on the function of each CER subclass and on the relation between CER lipid organisation and compo...

The barrier function of the stratum corneum (SC) is directly related to: (1) the nature and the composition of the lipids in the intercellular spaces and (2) the conformational order of the ceramides within this layer. The aim of this work was to determine Raman descriptors for the lateral packing, the conformation, and the structure of ceramides I...

Malignant melanoma (MM) is the most severe tumor affecting the skin and accounts for three quarters of all skin cancer deaths. Raman spectroscopy is a promising nondestructive tool that has been increasingly used for characterization of the molecular features of cancerous tissues. Different multivariate statistical analysis techniques are used in o...

Raman microspectroscopy allows probing subcellular compartments and provides a unique spectral fingerprint indicative of endogenous molecular composition. Although several spectroscopic cell studies have been reported on fixed samples, only few attempts concern single growing cells. Here, we have tested different optical substrates that would best...

The barrier function of the skin is related to the unique composition of the stratum corneum (SC) lipids and their complex structural arrangement. The high content of ceramides would seem to be ideally suited for the formation of ordered impermeable membrane. Skin penetration enhancers (PE) are molecules which reversibly remove the barrier resistan...

A digital automatic dewaxing method of Raman spectral im-ages acquired on paraffin-embedded human skin biopsies is proposed in this paper. This method is based on pre-processing steps specific to Raman spectra, on the estimation of the paraffin spectra by the Principal Component Analy-sis (PCA) and Independent Component Analysis (ICA), and on the e...

Confocal Raman microspectroscopy represents the advantage of giving structural and conformational information on samples without any destructive treatment. Recently, several studies were achieved to study the skin hydration, endogenous and exogenous molecules repartition in the skin using the confocal feature of this technique. Meanwhile, when work...

Skin is a multilayered organ which covers and protects the surface of human body by providing a barrier function against exogenous agents. Meanwhile, the efficacy of several topically applicated drugs is directly related to their penetration through the skin barrier. Several techniques are commonly used to evaluate the rate, the speed and the depth...

Human skin is directly exposed to different exogenous agents. Many research works have studied the diffusion, interactions, absorption mechanisms, and/or toxicity of these agents toward different cutaneous structures. With the use of living animals for such tests being more and more rejected; and the number of human volunteers being limited; differ...

Raman spectroscopy is a useful tool to investigate the molecular composition of biological samples. Source separation methods can be used to efficiently separate dense informations recorded by Raman spectra. Distorting effects such as fluorescence background, peak misalignment or peak width heterogeneity break the linear and instantaneous generativ...

Raman spectra provide wealthy but complex information about the chemical constituents of biological samples. Digital processing techniques are usually needed to extract the spectra of chemical constituents and their associated concentration profiles. However, spectral signatures may admit transformations from those recorded on pure constituents and...

Raman spectroscopy is employed to record spectra which highlight vibrational information of biological structures. These spectra provide useful information about molecular composition of a tissue. However, the tissues are usually embedded into paraffin for a preservation purpose. The Independent Component Analysis (ICA) technique can be used to num...

In the last few years, Raman spectroscopy has been increasingly used for the characterization of normal and pathological tissues. A new Raman system, constituted of optic fibers bundle coupled to an axial Raman spectrometer (Horiba Jobin Yvon SAS), was developed for in vivo investigations. Here, we present in vivo analysis on two tissues: human ski...

Vibrational spectroscopy is increasingly used for the investiga- tion of biological tissues: spectral analysis reveals hidden in- formation at microstructural and molecular levels. Moreover, in vitro and ex vivo applications have established the potential of these techniques for detecting and diagnosing different types of lesions. Several studies s...

Measuring Raman spectra of patient tissues, rapidly, in vivo and in real time, and allowing immediate diagnosis are challenges that have to be reached for a future clinical development of optical techniques. We present here examples of Raman spectra collected with a portable system on skin lesions and aortic tissues. Performances, but also limitati...

The paraffin embedding process enables to conserve biopsies for several years. However, the use of paraffinised tissues for spectroscopic investigations remains very restricted. This is due to the intense Raman peaks of paraffin that mask important vibrational information of the tissue in recorded spectra. Paraffinised tissues are usually chemicall...

This paper deals with a promising methodology for melanoma early diagnosis. Raman spectroscopy is used to record vibrational information of paraffinised tumoral tissues. Independent Component Analysis (ICA) is performed on Raman spectra to numerically deparaffinise spectra. Resulting deparaffinised spectra are used to extract discriminant informati...

FTIR microspectroscopy, in combination with cluster analysis, has been used to characterise skin tissues, in order to discriminate cancerous from non-cancerous ones. The main objective of this in vitro study was to demonstrate the applicability of infrared spectral imaging to separate, on paraffinised biopsies, pigmented nevi (benign skin lesions)...