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

R. F. Donnelly, Paul McCarron, R. Al-Kassas, A. Juzeniene, P. Juzenas, V. Iani, A. D. Woolfson, J. Moan

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.
LanguageEnglish
Pages55-70
JournalBiopharmaceutics and Drug Disposition
Volume30
Issue number2
DOIs
Publication statusPublished - 2009

Fingerprint

Aminolevulinic Acid
Gels
Propylene Glycol
Skin
Neoplasms
Drug Stability
Phototoxic Dermatitis
Suppositories
Skin Temperature
Photochemotherapy
Growth
protoporphyrin IX
Lasers
Fluorescence
Clinical Trials

Cite this

Donnelly, R. F. ; McCarron, Paul ; Al-Kassas, R. ; Juzeniene, A. ; Juzenas, P. ; Iani, V. ; Woolfson, A. D. ; Moan, J. / Influence of Formulation Factors on PpIX Production and Photodynamic Action of Novel ALA-loaded Microparticles. In: Biopharmaceutics and Drug Disposition. 2009 ; Vol. 30, No. 2. pp. 55-70.
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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.",
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Influence of Formulation Factors on PpIX Production and Photodynamic Action of Novel ALA-loaded Microparticles. / Donnelly, R. F.; McCarron, Paul; Al-Kassas, R.; Juzeniene, A.; Juzenas, P.; Iani, V.; Woolfson, A. D.; Moan, J.

In: Biopharmaceutics and Drug Disposition, Vol. 30, No. 2, 2009, p. 55-70.

Research output: Contribution to journalArticle

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AU - McCarron, Paul

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AU - Juzeniene, A.

AU - Juzenas, P.

AU - Iani, V.

AU - Woolfson, A. D.

AU - Moan, J.

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