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Novel patch-based systems for the localised delivery of ALA-esters

Biomedical Sciences Research Institute Computer Science Research Institute Environmental Sciences Research Institute Nanotechnology & Advanced Materials Research Institute

Morrow, Desmond I. J., McCarron, P. A., Woolfson, A. David, Juzenas, Petras, Juzeniene, Asta, Iani, Vladimir, Moan, Johan and Donnelly, Ryan F. (2010) Novel patch-based systems for the localised delivery of ALA-esters. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, 101 (1). pp. 59-69. [Journal article]

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DOI: 10.1016/j.jphotobiol.2010.06.012

Abstract

In photodynamic therapy (PDT) a combination of visible light and a sensitising drug causes the destruction of selected cells. Aminolaevulinic acid (ALA) has been widely used in topical PDT for over 15 years. However, ALA does not possess favourable physicochemical properties for skin penetration. Consequently, the clearance rates for difficult to treat lesions, such as nodular basal cell carcinomas are relatively low. For the first time, equimolar concentrations of ALA, methyl-ALA (m-ALA) and hexyl-ALA (h-ALA) have been incorporated into a bioadhesive patch-based system. In vitro penetration studies into excised porcine skin revealed that ALA patches containing relatively high loadings (226.7 mu mol cm(-2)) were associated with significantly greater tissue concentrations (70.7 mu mol cm(-3)) than patches containing m-ALA (16.3 mu mol cm(-3)) or h-ALA (17.4 mu mol cm(-3)). ALA was also found to be the most efficient inducer of protoporphyrin (PpIX) fluorescence in mice, in vivo (maximum mean fluorescence: ALA = 236.2 a.u., m-ALA = 175.1 au., h-ALA = 193.5 a.u.). However, when the lipophilic hexylester was formulated in a pressure sensitive adhesive (PSA) patch, significantly higher PpIX levels were achieved compared to all bioadhesive systems tested. Of major importance, PSA patches containing relatively low h-ALA loadings induced high PpIX levels, which were localised to the application area. This study has highlighted the importance of rational selection of both the active agent and the delivery system. Bioadhesive preparations containing ALA are ideal for delivery to moist environments; whereas h-ALA-loaded PSA systems may facilitate enhanced delivery to dry areas of skin. In addition, owing to the relatively low loadings of h-ALA required in PSA patches, the costs of clinical PDT may potentially be reduced. (C) 2010 Elsevier B.V. All rights reserved.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Pharmacy and Pharmaceutical Science
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Pharmaceutical Science and Practice
ID Code:17122
Deposited By:Professor Paul McCarron
Deposited On:17 Feb 2011 14:55
Last Modified:26 Nov 2012 11:44

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