Biophysical characterisation of the skin at a molecular level

This thesis investigates the skin barrier properties at a molecular level and possible methods to enhance model drug (niacinamide) permeation across model membranes and human skin. These can serve to improve the skin barrier function, understanding biophysical properties of the skin and more importantly developing a healthier and better appearance of the skin. In normal skin, stratum corneum desquamation and maturation are a carefully balanced process by the underlying rate of proliferation. The corneodesmosomes are degraded by serine proteases such as kallikrein 5 and kallikrein 7. This progressive process is precisely controlled to maintain skin integrity and TransEpidermal Water Loss (TEWL). As a result, the primary object is to develop and validate minimally invasive techniques to characterise and examine the skin barrier function. The skin's barrier properties is investigated at a molecular level as a function of depth, anatomical site, age, gender and ethnicity using relatively non-invasive techniques in vivo. Further experimental work involved understanding the influence of the UK's most prescribed and cheapest cream 'Aqueous Cream B.P.' on the SC. The techniques indicate that application of Aqueous Cream B.P. as a leave-on moisturiser can be damaging to the skin by reducing the corneocyte surface area, decreasing cell maturities, increasing selected desquamatory and inflammatory serine protease activities and TEWL. Using the techniques developed as well as confocal Raman spectrometry, the SC was investigated after application of a cosmetic and pharmaceutical active niacinamide in a range of formulations. The results recommend application of moisturiser containing niacinamide can improve the skin's barrier function. Finally, the permeation of niacinamide in vitro through model synthetic membrane and human skin under infinite and clinical doses were investigated. The results were then compared with the in vivo permeation of niacinamide. A range of formulations together with commercially available products that contain similar amount of the model drug were examined. There were no correlation between the flux of niacinamide through synthetic membranes and human skin. These techniques can effectively be applied in vivo to examine the skin barrier function at a molecular level and investigate the role of various formulations on the skin's barrier integrity. These assist the development of 'smarter' and more cost-effective pharmaceutical or cosmetic dermal formulations.EThOS - Electronic Theses Online ServiceGBUnited Kingdo