Estimation of In Vivo Water Content of the Stratum Corneum from Electrical Measurements

In vivo water content in the epidermal stratum corneum can be estimated by means of low frequency susceptance measurements. In the in vitro calibration necessary to find the in vivo water content, the stratum corneum will have a uniform distribution of water across its thickness. However, in vivo stratum corneum has an increasing water concentration profile from the outermost towards the innermost parts. This paper will investigate the possibility of estimating the equilibrium water content in the in vivo stratum corneum non-invasively from electrical susceptance measurements. Given a known shape of the water concentration profile in the in vivo stratum corneum and the dependence of susceptance on the water content, it is possible to calculate the water content in vivo based on analytically derived expressions for the water concentration profile. A correspondence between in vivo and in vitro water content needed for this purpose is also established

Review of Advances in the Measurement of Skin Hydration Based on Sensing of Optical and Electrical Tissue Properties

The presence of water in the skin is crucial for maintaining the properties and functions of the skin, in particular its outermost layer, known as the stratum corneum, which consists of a lipid barrier. External exposures can affect the skin’s hydration levels and in turn, alter its mechanical and physical properties. Monitoring these alterations in the skin’s water content can be applicable in clinical, cosmetic, athletic and personal settings. Many techniques measuring this parameter have been investigated, with electrical-based methods currently being widely used in commercial devices. Furthermore, the exploration of optical techniques to measure hydration is growing due to the outcomes observed through the penetration of light at differing levels. This paper comprehensively reviews such measurement techniques, focusing on recent experimental studies and state-of-the-art devices

Design and Analysis of a Continuous and Non-Invasive Multi-Wavelength Optical Sensor for Measurement of Dermal Water Content

Dermal water content is an important biophysical parameter in preserving skin integrity and preventing skin damage. Traditional electrical-based and open-chamber evaporimeters have several well-known limitations. In particular, such devices are costly, sizeable, and only provide arbitrary outputs. They also do not permit continuous and non-invasive monitoring of dermal water content, which can be beneficial for various consumer, clinical, and cosmetic purposes. We report here on the design and development of a digital multi-wavelength optical sensor that performs continuous and non-invasive measurement of dermal water content. In silico investigation on porcine skin was carried out using the Monte Carlo modeling strategy to evaluate the feasibility and characterize the sensor. Subsequently, an in vitro experiment was carried out to evaluate the performance of the sensor and benchmark its accuracy against a high-end, broad band spectrophotometer. Reference measurements were made against gravimetric analysis. The results demonstrate that the developed sensor can deliver accurate, continuous, and non-invasive measurement of skin hydration through measurement of dermal water content. Remarkably, the novel design of the sensor exceeded the performance of the high-end spectrophotometer due to the important denoising effects of temporal averaging. The authors believe, in addition to wellbeing and skin health monitoring, the designed sensor can particularly facilitate disease management in patients presenting diabetes mellitus, hypothyroidism, malnutrition, and atopic dermatitis

Novel Thermal Analytical Techniques to Characterize Drugs and Drug Delivery

This thesis encompasses three significant projects. The study includes the characterization and evaluation of the properties of a commercial contraceptive transdermal patch, Ortho Evra® by Dielectric Analysis and Differential Scanning Calorimetry (DSC). This study helps in monitoring the mobility of the drug and transport properties by Isothermal and Scanning Dielectric Analysis as a function of temperature and frequency. The drugs in this product are norelgestromin and ethinyl estradiol. DSC was used to detect any crystalline character of the drugs by their fusion properties. Having no melting endotherm and detecting a glass transition temperature suggested that the drugs in the patches were amorphous. The amorphous form of the drug has more bioavailability. The isothermal DEA a plot of Log frequency vs. reciprocal temperature (K) revealed two critical modulating frequencies at body temperature 37°C for the two API drugs with DEA peak frequencies at 460 and 560 Hz. The main project includes studying the polarization of macro and micro molecular liquid drugs by Dielectric Analysis, B-Cell (a customized isothermal dielectric device) and Differential Scanning Calorimetry. This study demonstrated in vitro transport of selected non-ionic high (e.g. insulin) and low (e.g. Diphenhydramine) molecular weight drugs through excised biological tissue membranes using alternating current (AC) electrokinetics. This new technique of the drug delivery system enhances benefits over systemic oral therapies, in which clinically sufficient quantities of the active ingredient do not reach the intended target organ and/or use of the drugs result in serious side effects. An optimally-tuned low-voltage applied AC electrical field has been found capable of inducing polarization and delivering micro and macromolecules through a biological membrane. The relationships between factors such as delivery time, AC voltage amplitude and frequency, and transported drug concentration were investigated. A factorial design was used to estab

Epidermal sensors for monitoring skin physiology

Wearable sensors are revolutionizing personalised healthcare and have continuously progressed over the years in both research and commercialization. However, most efforts on wearable sensors have been focused on tracking movement, spatial position and continuous monitoring of vital signs such as heart rate or respiration rate. Recently, there is a demand to obtain biochemical information from the body using wearables. This demand stems from an individuals’ desire for improved personal health awareness as well as the drive for doctors to continuously obtain medical information for a patients’ disease management. Epidermal sensors are a sub-class of wearable sensors that can intimately integrate with skin and have the potential for monitoring physical changes as well as detecting biomarkers within skin that can be related to human health. The holy grail for these types of sensors is to achieve continuous real-time monitoring of the state of an individual and the development of these sensors are paving the way towards personalised healthcare. However, skin is highly anisotropic which makes it challenging to keep epidermal sensors in consistent contact with skin. It is important that these sensors remain in contact with skin in order to measure its electrical properties and acquire high fidelity signals. The key objective of this thesis is to develop thin conformable, stretchable epidermal sensors for tracking changes in skin physiology. The initial iteration of the screen printed epidermal sensor comprised of a flexible silver film. Impedance spectroscopy was used to understand the electrical signals generated on skin and it was used to measure relative changes due to varying water content. However, this iteration was more suited for single use. The next chapters explore different ink formulations and adherence methodologies to enhance the epidermal sensors adherence to skin. Impedance spectroscopy was used to characterise the electrical signals from these different epidermal sensor iterations, while tensile testing and on-body assessment was used to characterise its mechanical properties. The final chapter focused on investigating the use of phenyl boronic acid (PBA) functionalized hydrogels to modify the epidermal sensor with responsive hydrogel materials to enable chemical sensing of analytes relevant to skin physiology. Impedance spectroscopy was used to characterise and understand the electrical signals generated by the binding interaction of the PBA and analytes using the sensor. Overall, the work demonstrates the challenges of developing these epidermal sensors as well as presenting their potential for continuous monitoring of human skin in the future

Monitoring Dermal Penetration and Permeation Kinetics of Topical Products; the Role of Raman Microspectroscopy

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 mathematical models of diffusion, of varying degrees of complexity, and are commonly measured by Franz cell diffusion, in vitro, and tape stripping, in vitro or in vivo, techniques which are recognised by regulatory bodies for commercialisation of dermally applied products. These techniques do not directly provide chemically specific measurement of the penetration and/or permeation of formulations in situ, however. Raman microspectroscopy provides a non-destructive, non-invasive and chemically specific methodology for in vitro, and in vivo investigations, in-situ, and can provide a powerful alternative to the current gold standard methods approved by regulatory bodies. This review provides an analysis of the current state of art of the field of monitoring dermal penetration and permeation kinetics of topical products, in vitro and in vivo, as well as the regulatory requirements of international guidelines governing them. It furthermore outlines developments in the analysis of skin using Raman microspectroscopy, towards the most recent demonstrations of quantitative monitoring of the penetration and permeation kinetics of topical products in situ, for in vitro and in vivo applications, before discussing the challenges and future perspectives of the field

Application of biophysics and bioengineering to the assessment of skin barrier function

Atopic dermatitis (AD) is one of the most common inflammatory skin diseases. The cause of AD is multifactoral and it is affected by both genetic and environmental factors. Of all the causes of potential barrier defects, the lowered amino-acid derived natural moisturizing factor (NMF) in the stratum corneum (SC), especially associated with a known filaggrin mutation, shows the strongest link to AD. As a result, quantification of NMF in the SC in both healthy and compromised SC is the principal aim of this thesis. Because tape stripping is a key technique used to harvest the SC, a novel imaging method to measure the amount of SC per tape strip was validated. This method offers rapid, simple and reproducible SC quantification. It shows good correlation with existing gravimetric and infrared absorption methods and may provide a better standard method in the future. The tape-stripping extraction of NMF showed an abundant SC ‘reservoir’ of the constituents in healthy skin. Iontophoretic extraction of NMF was highly dependant upon molecular properties, particularly charge and concentration. In general, charged NMF constituents were easily extracted by reverse iontophoresis, whereas iontophoresis only offered modest enhancement of zwitterionic species. Quantification of NMF at different body sites, specifically forehead and forearm, showed similar profiles. However, forehead SC was thinner, and in general contained a lower total amount of NMF and less-ordered lipids. Forehead SC may therefore be considered a less competent barrier. A 3-week application of 0.1% w/v sodium lauryl sulphate (SLS) to healthy volunteers was used to model damaged skin similar to that in AD and chronic irritant contact dermatitis. The SC barrier post-treatment showed significantly reduced NMF, substantial lipid disordering, and the presence of immature corneocytes. The methods employed were sufficiently sensitive to detect these changes. In particular, the NMF components present at high levels in the SC may be useful, potential markers for skin ‘health’ and for its resistance to irritant chemicals.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Novel Thermal Analytical Techniques to Characterize Drugs and Drug Delivery

This thesis encompasses three significant projects. The study includes the characterization and evaluation of the properties of a commercial contraceptive transdermal patch, Ortho Evra® by Dielectric Analysis and Differential Scanning Calorimetry (DSC). This study helps in monitoring the mobility of the drug and transport properties by Isothermal and Scanning Dielectric Analysis as a function of temperature and frequency. The drugs in this product are norelgestromin and ethinyl estradiol. DSC was used to detect any crystalline character of the drugs by their fusion properties. Having no melting endotherm and detecting a glass transition temperature suggested that the drugs in the patches were amorphous. The amorphous form of the drug has more bioavailability. The isothermal DEA a plot of Log frequency vs. reciprocal temperature (K) revealed two critical modulating frequencies at body temperature 37°C for the two API drugs with DEA peak frequencies at 460 and 560 Hz. The main project includes studying the polarization of macro and micro molecular liquid drugs by Dielectric Analysis, B-Cell (a customized isothermal dielectric device) and Differential Scanning Calorimetry. This study demonstrated in vitro transport of selected non-ionic high (e.g. insulin) and low (e.g. Diphenhydramine) molecular weight drugs through excised biological tissue membranes using alternating current (AC) electrokinetics. This new technique of the drug delivery system enhances benefits over systemic oral therapies, in which clinically sufficient quantities of the active ingredient do not reach the intended target organ and/or use of the drugs result in serious side effects. An optimally-tuned low-voltage applied AC electrical field has been found capable of inducing polarization and delivering micro and macromolecules through a biological membrane. The relationships between factors such as delivery time, AC voltage amplitude and frequency, and transported drug concentration were investigated. A factorial design was used to estab