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Title: Characterisation and formulation of hexamidine salts and in-vivo profiling of stratum corneum interleukin-1
Author: Parisi, N.
ISNI:       0000 0004 8503 7506
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2016
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The extraordinary structure and properties of the skin provide us with a physico-mechanical barrier which protects us from a whole array of xenobiotics and prevents us from losing water, thus allowing human life in a non-aqueous environment. Therefore, the preservation of this vital barrier is an important aspect of an individual's healthcare and research into active ingredients which can enhance the barrier properties of the skin and contribute to skin health and appearance is an evergreen field. In this context, hexamidine (HEX) has recently been shown to affect a series of biomarkers of barrier function, inflammatory status and turnover of the skin which are ultimately related to its moisturisation and aging. As a result, two of its salts, hexamidine diisethionate (HEX D) and hexamidine dihydrochloride (HEX H), were selected for the present work and a comprehensive characterisation of their physicochemical properties was undertaken. These preparatory studies were fundamental for the subsequent rational design of simple topical formulations with the potential to deliver both actives into the skin. The formulation development was accomplished by means of well-established in-vitro techniques, namely Franz diffusion cell permeation and mass balance studies. In addition, chemical penetration enhancers were used to promote the topical delivery of HEX D and HEX H. Once the formulations were successfully designed, tape stripping, transepidermal water loss (TEWL), protein content measurement and multi-analyte profiling (xMAP® ) technology were combined so as to develop a set of techniques which allows the interrogation of the barrier function and the inflammatory status of the skin in-vivo. The stratum corneum depth profiles of interleukin-1 receptor antagonist (IL-1RA), interleukin-1 alpha (IL-1α) and IL-1RA:IL-1α ratio were then investigated on healthy subjects, thus confirming that this set of techniques has the potential to be applied for testing the effects of the novel HEX D and HEX H formulations in-vivo.
Supervisor: Lane, M. E. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available