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Title: Towards a nanomedicine-based broad-spectrum topical virucidal therapeutic system
Author: Houston, David
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2011
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The health benefits of the fruit of Punica granatum (pomegranate) have been recognised for many centuries. This thesis tested the hypothesis that a potent novel antimicrobial system could be developed based upon the activity of pomegranate rind extract (PRE), particularly when combined with a potentiating agent, and focussed on studying activity against Herpes simplex virus, types 1 and 2 (HSV-1 and HSV-2). High potentiated virucidal action of PRE against HSV-1 was observed when ferrous sulphate (FeSO4) was added; however, this activity diminished rapidly and also gave rise to an unsightly black byproduct. Data was obtained suggesting this was linked to the rapid oxidation of ferrous to ferric (Fe (II) to Fe (III)); however, no such oxidation was indicated when zinc sulphate (ZnSO4) was added instead, prompting an exploration of the effects of PRE + ZnSO4 combination on HSV. The potentiation of PRE by ZnSO4 in virucidal mode was comparable to that observed with FeSO4 (at the concentration examined for both metal salts). More in-depth investigation of the potentiation of PRE and ZnSO4 achieved over a 9000 fold increase in viral destruction in comparison to either agent alone. This activity was not transient and did not produce a (black) byproduct. Other salts of Zn (II) generally performed similarly to ZnSO4, with the main exception of ZnO which was too insoluble in water to test. When the antiviral properties of PRE were examined, the results were again potent and comparable to Aciclovir, the established treatment for Herpes simplex infections. Furthermore, PRE demonstrated even greater potency against Aciclovir-resistant HSV-2. When applied to ex vivo skin, PRE produced a 66% reduction in the level of cyclooxygenase-2 (COX–2) - an important inflammatory mediator - with the presence of ZnSO4 having no effect. PRE and ZnSO4 were formulated as a stable hydrogel, which was able to effectively deliver the biologically active compounds through the epidermal, buccal and vaginal membranes to the epidermal/dermal interface - the major sites of HSV-1 and HSV-2 vesicular clusters during a clinical infection.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: RM Therapeutics. Pharmacology