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Influence of Formulation Factors on PpIX Production and Photodynamic Action of Novel ALA-loaded Microparticles

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

Donnelly, R. F., McCarron, Paul, Al-Kassas, R., Juzeniene, A., Juzenas, P., Iani, V., Woolfson, A. D. and Moan, J. (2009) Influence of Formulation Factors on PpIX Production and Photodynamic Action of Novel ALA-loaded Microparticles. Biopharmaceutics & drug disposition, 30 (2). pp. 55-70. [Journal article]

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DOI: 10.1002/bdd.645

Abstract

A novel 5-aminolevulinic acid (ALA)-containing microparticulate system was produced recently, based on incorporation of ALA into particles prepared from a suppository base that maintains drug stability during storage and melts at skin temperature to release its drug payload. The novel particulate system was applied to the skin of living animals, followed by study of protoporphyrin IX (PpIX) production. The effect of formulating the microparticles in different vehicles was investigated and also the phototoxicity of the PpIX produced using a model tumour. Particles formulated in propylene glycol gels (10% w/w ALA loading) generated the highest peak PpIX fluorescence levels in normal mouse skin. Peak PpIX levels induced in skin overlying subcutaneously implanted WiDr tumours were significantly lower than in normal skin for both the 10% w/w ALA microparticles alone and the 10% w/w ALA microparticles in propylene glycol gels during continuous 12 h applications. Tumours not treated with photodynamic therapy continued to grow over the 17 days of the anti-tumour study. However, those treated with 12 h applications of either the 10% w/w ALA microparticles alone or the 10% w/w ALA microparticles in propylene glycol gel followed by a single laser irradiation showed no growth. The gel formulation performed slightly better once again, reducing the tumour growth rate by approximately 105%, compared with the 89% reduction achieved using particles alone. Following the promising results obtained in this study, work is now going on to prepare particle-loaded gels under GMP conditions with the aim of initiating an exploratory clinical trial. Copyright (C) 2009 John Wiley & Sons, Ltd.

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:1124
Deposited By:Professor Paul McCarron
Deposited On:21 Oct 2010 15:30
Last Modified:26 Nov 2012 11:48

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