Understanding the delivery of actives to the skin

Skin diseases such as eczema and dermatitis represent a major public health problem in the UK today with a significant impact on the quality of life of patients, particularly young children. The majority of topical preparations which are used in the management of these conditions 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 more effective products, with a lower cost to patients and government. Permeation of an active through human skin is highly formulation or vehicle dependent. The problem in understanding the barrier function of skin and in assessing the mechanisms of action of penetration modifiers in formulations is that it is difficult to study the pathway of the active or the modifier. Specifically, it is not possible to determine how the presence of one influences the transport of the other in real time. The UCL Skin group has recently shown that actives may be depth profiled in skin in vivo with Confocal Raman Spectroscopy (CRS). Unilever have advanced the use of deuterated formulation components to separate their signal from endogenous skin lipids. These findings as well as other recent studies have opened up significant new opportunities in understanding mass transport in skin. The objectives of this multidisciplinary PhD project are to exploit the unique ability of CRS to provide molecular level insights into skin transport of both actives and formulation components. These important issues will be elucidated in a novel manner by collecting, simultaneous, spatially resolved chemical information. Conventional in vitro diffusion studies will be used to validate the in vivo results obtained from CRS. A range of actives commonly employed in topical products will be selected for study. These will span a range of physicochemical properties (partition and solubility) and the effects of specific materials on their skin transport will be examined. Measurement aspects in UCL will be aligned with an internal Unilever programme of modelling delivery in skin. A major challenge will be the accurate interpretation of spectral data generated from the chemically heterogeneous skin surface interacting with complex formulations. Novel chemometric treatment of spectra will be used to enable more effective analysis compared with traditional methods based on single peaks which have severe limitations in complex systems. Overall, the outputs of the project will contribute to an advanced model for predicting skin penetration which will have relevance to other government and research stakeholders.
In particular, this project is well aligned with the following EPSRC research themes of maintaining interests:
- Analytical science - Determination of skin disposition of actives by advanced spectroscopic approaches
- Biophysics and soft matter physics - fundamental understanding of complex fluids and soft solids: colloids, polymers, gels, liquid and interactions with biological interfaces
- Chemical biology and biological chemistry - Application of chemical techniques for the understanding of biological processes and the synthesis of biologically active and biological molecules.
- Manufacturing technologies - focuses on key enabling technologies that will allow manufacturing processes, products and systems to function with high precision, efficiency, reliability and repeatability.