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Title: An investigation into the influence of local barometric stress upon xenobiotic percutaneous penetration
Author: Dias Pereira Inacio, Ricardo Alexandre
ISNI:       0000 0004 5990 8064
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2015
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Local barometric pressure changes at the apical surface of the skin have been reported to alter the mechanical and physiological properties of the cutaneous tissue. However, how skin changes induced by barometric pressure alter percutaneous penetration require further investigation. The aim of this study was to understand the effects of local barometric pressure changes upon cutaneous drug delivery with a view to understand if such an approach could be used to design a novel medicinal product. To accomplish this, one of the most widely used test systems for studying in vitro skin permeability, the Franz diffusion cell, was adapted to operate under sub-atmospheric pressure. Three relevant agents (tetracaine, diclofenac diethylamine and aciclovir) were selected, based upon their different physicochemical properties, and a suitable analytical method was developed for each molecule. The model agents were shown to aggregate in solution and the process of aggregation appeared to retard penetration into the skin. In vitro hypobaric driven delivery was shown to be an effective means to achieve ‘targeting’ of diclofenac diethylamine and aciclovir within the epidermal tissue after topical application of the aggregated agents. The calculated epidermal ‘targeting’ potential was 4 and 1.4 for each model agent, respectively. The mechanical and morphological changes in the hypobaric stressed skin showed that the ‘targeted’ drug deposition to the epidermal layer was accompanied by an enlargement of the follicular infundibula (p < 0.001), reduced corneocyte size (p < 0.001) and skin thinning (p < 0.05). These findings suggested that both enhanced follicular and passive stratum corneum transport played a role in the manner which hypobaric pressure improved cutaneous penetration. Local hypobaric stress application to the skin was also shown to induce a haemodynamic response (i.e. a significant increase in blood flow (p < 0.001)), which together with the ability to alter skin drug diffusion significantly enhanced cutaneous and systemic bioavailability (p < 0.01) of a model macromolecule. These results demonstrated that the application of topical barometric stress represented a promising technology to deliver molecules into the skin and it was thought worthy of further evaluation.
Supervisor: Jones, Stuart Allen ; Keeble, Julie Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available