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Starr, Nichola (2017) Investigating native and exogenous compounds within skin tissue. PhD thesis, University of Nottingham.

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Abstract

The skin is the most extensive and accessible organ in the human body. It efficiently provides a barrier to an external hostile environment whilst maintaining and regulating fundamental physiological functions. The sophisticated and complex nature of this natural barrier requires continued analytical advancement to offer further insight into both its biological mechanisms and how to target the delivery of compounds through it. This work presents the use of a recently emerging technique in the field of skin research, time of flight - secondary ion mass spectrometry (ToF-SIMS), to investigate the presence of both native and exogenous compounds in skin tissue from samples collected both in vivo and ex vivo.

Subtle changes to the stratum corneum lipid composition have been shown to exert significant effects on the barrier properties of the skin and are associated with numerous skin disorders. The analysis of these lipid species and factors affecting their composition, both internal and external, is therefore a vital area of research. Using ToF-SIMS, this work has conducted an examination of changes to this lipid composition that have resulted from aging of the skin. This has been achieved by undertaking extensive development of a recently proposed surface analysis method to analyse sequential tape strips of stratum corneum. This study was unprecedented in demonstrating that ToF-SIMS could obtain information on human skin from samples collected in vivo. Changes in the levels of both cholesterol sulfate and long chain fatty acids were observed as a consequence of both intrinsic and extrinsic aging, offering confirmatory evidence to previously theorised skin aging mechanisms.

Research relating to the effective permeation of compounds across this skin barrier is also of upmost importance, both to the pharmaceutical and cosmetic industries, to enable the design of new topical formulations for skin delivery. Currently employed methods to assess the permeation of a compound are heavily focused on dermal delivery, with limited information obtained on the effectiveness of a compound to permeate into the upper layers of the skin. This research has therefore pioneered a dynamic SIMS method to conduct depth profile analysis of ex vivo porcine skin tissue, enabling the permeation of exogenous compounds to be monitored as a function of skin depth.

This work is novel in successfully producing 3D spatially resolved chemical profiles of exogenous compounds within biological tissue using ToF-SIMS. The permeation of four different vitamin C related compounds, popular ingredients in anti-aging cosmetic formulations, were assessed using this method, highlighting a significant difference in permeation efficiency between them. An investigation into the delivery of ascorbic acid to the skin from various different formulations was also achieved, highlighting a permeation enhancing effect from delivery via a novel supramolecular gel formulation. The method developed for surface analysis was also successfully applied to monitor the permeation of ascorbic acid through human stratum corneum following in vivo application of an ‘off-the-shelf’ cosmetic product.

Item Type:	Thesis (University of Nottingham only) (PhD)
Supervisors:	Scurr, David Barrett, David
Keywords:	ToF-SIMS, skin, analytical, stratum corneum, topical products, lipids, surface analysis, depth profiling, tape stripping, human, in vivo, porcine, ex vivo, cosmetics
Subjects:	Q Science > QP Physiology > QP1 Physiology (General) including influence of the environment
Faculties/Schools:	UK Campuses > Faculty of Science > School of Pharmacy
Item ID:	39139
Depositing User:	Starr, Nichola
Date Deposited:	17 Jul 2017 04:40
Last Modified:	08 May 2020 12:15
URI:	https://eprints.nottingham.ac.uk/id/eprint/39139

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