Bashir, Saqib Jawaid (2006) The skin barrier: Tape stripping studies. MD thesis, University of Glasgow.
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Abstract
The skin, being an exposed organ, is an easy site to access for research. However, standard interventions, such as a biopsy, leave the skin scarred and are logistically cumbersome. Therefore, non-invasive methods are preferable providing reliable in vivo data can be obtained. The study of the skin barrier is particularly suited to non-invasive techniques, as the ability of the skin to allow molecules to permeate is a dynamic process best seen in living tissue. A widely utilized method is the application of adhesive tapes to the skin. These tapes, when removed, take with them a small amount of stratum corneum that is adherent: this can be studied further, as can the remaining skin at the stripping site. Typical studies performed in this way include studies of "drugs reservoirs" in the stratum corneum (where lipophilic compounds accumulate), studies of the skin barrier to water and other substances, studies of transdermal drug delivery and studies of wound healing and stratum corneum physiology. There is no standardized method for tape stripping, resulting in confusion over technique and difficulty in interpreting other workers' data. Recently there have been attempts to improve the methodology. One such improvement by this laboratory has been the development of a method to quantify the exact amount of stiatum comeum on each tape. This information is expected to advance the use of the tape stripping model considerably particularly because other variables can now be measured against stratum corneum mass and depth. It is the aim of this thesis to take that work forward. The aim of this thesis is to build on a new model of stratum corneum tape stripping and demonstrate its usefulness as a method of studying the stratum corneum, both physiologically and phannacologically. Each of the studies performed has advanced the existing database of knowledge in this field. Study 1 has demonstrated that a variety of tapes can be successfully and generally equivalently used to study skin water kinetics. It has provided a database of information on tape stripping for future investigators and re-calculated water kinetics using the new quantitative data. In addition, this study has identified that a proportion of the population do not display increased transepidermal water loss despite significant barrier damage. This implies that the sheer mass of stratum corneum alone cannot explain the skin barrier to water, but rather there must be other factors such as the proportion of different types of lipids that must be responsible for this. Study 2 has, for the first time, demonstrated a quantitative method to assess the efficacy of keratolytic drugs. In addition, it has refuted a commonly held premise that acids applied to the skin must be at a pH near their pKa in order to retain their efficacy. In fact, this thesis shows that such practice results in increased skin irritation but no increase in efficacy, compared to less acidic preparations of the same acid. This data will allow those who formulate such drugs to make less irritating preparations. Study 3 has, for the first time, localized the acid mantle in vivo in human skin and also confirmed that this acid mantle is distinct from skin surface acidity. Also, this study has discovered a zone in the stratum corneum where pH is almost stable for 1?m, consistently between subjects, suggesting that common metabolic processes are taking place at this site. This information is of use to those who formulate drugs for transdermal delivery, to the study of skin metabolism and to the study of diseases with altered skin pH, such as atopic dermatitis. (Abstract shortened by ProQuest.).
Item Type: | Thesis (MD) |
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Qualification Level: | Doctoral |
Keywords: | Medicine, Pharmaceutical sciences |
Colleges/Schools: | College of Medical Veterinary and Life Sciences |
Supervisor's Name: | Mackie, Prof. Rona and Maibach, Prof. Howard I. |
Date of Award: | 2006 |
Depositing User: | Enlighten Team |
Unique ID: | glathesis:2006-71397 |
Copyright: | Copyright of this thesis is held by the author. |
Date Deposited: | 10 May 2019 10:49 |
Last Modified: | 21 May 2021 13:20 |
URI: | https://theses.gla.ac.uk/id/eprint/71397 |
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