Biophysical and spectroscopic analysis of skin

There is an urgent need to provide a molecular level insight into mechanisms of topical and transdermal active delivery as a function of anatomic site and skin health. The majority of topical preparations today typically deliver only a few per cent of active to the skin. If the reasons underlying this inefficient performance were better understood this would allow the design of better products with a lower cost. The use of Franz diffusion cell studies for studying permeation of actives through skin is well established. However, very few of these in-vitro studies have measured the amount of active which permeates through tissue from different body sites or through compromised or diseased skin sites (e.g. dandruff). Also ideally in-vivo studies should be done to confirm any findings. Such information is crucial in understanding the pathways of permeation of actives and the factors that influence this transport process. The PIs have demonstrated that new opportunities exist for profiling drug and excipients with Confocal Raman spectroscopy. The use of deuterated solvents to separate their signal from endogenous skin lipids has also been advanced by the applicants. CRS is a completely non-invasive technique and has the potential to answer fundamental questions about the healthy and diseased skin barrier.
The aims and objectives of the proposed multidisciplinary work are to exploit the unique advantages of CRS to understand chemical heterogeneity of skin as a function of anatomic site and skin health. The study will elucidate these important issues in a novel manner by collecting simultaneously spatially resolved chemical information. The broader goal is to facilitate the use of CRS for skin research by revealing the underlying mechanisms of mass transport through the various strata of the skin. The accurate interpretation of spectral data generated from a chemically heterogeneous skin surface interacting with complex formulations requires careful data analysis. The application of novel chemometric data treatments will enable better and efficient data analysis compared to the traditional methods based on single peaks which have severe limitations in complex systems methods based on single peaks which have severe limitations in complex systems. The PI's have expertise in this area and have applied this before however, further work is required. As well as trainining in CRS, chemometrics and advanced data analysis the student will be trained in the use of in vitro models of drug transport and biophysical methods to interrogate skin including trans-epidermal water loss and capacitance imaging. The findings of the project are expected to lead to a better understanding of the fate of actives and excipients in skin and ultimately to the development of better topical formulations.

The work to be carried out at Procter & Gamble is as follows:
1. Establish in vitro skin models that are validated with biophysical methods including Trans- epidermal water loss measurement and capacitance testing.
2. Obtain skin penetration profiles via Raman spectroscopy.
3. Develop algorithms for prediction of skin uptake from in vitro data.