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Aminolaevulinic acid diffusion characteristics in 'in vitro' normal human skin and actinic keratosis: implications for topical photodynamic therapy

McLoone, N., Donnelly, R. F., Walsh, M., Dolan, O. M., McLoone, S., McKenna, K. and McCarron, P. A. (2008) Aminolaevulinic acid diffusion characteristics in 'in vitro' normal human skin and actinic keratosis: implications for topical photodynamic therapy. Photodermatology Photoimmunology & Photomedicine, 24 (4). pp. 183-190. [Journal article]

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Abstract

Background: The response rate of aminolaevulinic acid (ALA)-based photodynamic therapy (PDT) in certain subtypes of actinic keratosis (AK), such as hypertrophic and hyperkeratotic lesions, is variable, an effect attributable to a supposed lack of ALA penetration. A detailed and depth-related profile of spatial ALA permeation in AK following drug administration would lead to a greater understanding of concentrations achievable before protoporphyrin IX biosynthesis and subsequent PDT. Methods: ALA penetration through excised normal human skin (NS) and AK lesions was evaluated using a cryostatic sectioning technique and radio-isotope counting following drug delivery using a novel, bioadhesive patch, loaded with 19, 38 or 50 mg/cm(2) ALA. Results: Distinct differences in ALA concentration with respect to depth between AK and NS samples were shown, particularly within the superficial layers of the tissue structure, down to a depth of 1.0 mm. Patch application times were shown to influence ALA concentrations in tissue, but there was no clear correlation between ALA penetration in AK lesions taken from different body locations and from patients of different age. Similarly, the thickness of stratum corneum was not related to the ALA distribution profiles. Conclusions: Sizable variation in ALA concentration was a prominent feature of profiles through AK lesions, which may explain the variation of observed protoporphyrin IX production seen in the clinical implementation of AK PDT. That said, the results of this study show sufficient ALA penetration to a depth of 1.0 mm, which should be satisfactory for successful treatment of the majority of non-hyperkeratotic, hypertrophic AK using patch-based delivery methods.

Item Type:Journal article
Keywords:None
Faculties and Schools:Faculty of Life and Health Sciences > School of Pharmacy and Pharmaceutical Science
Faculty of Life and Health Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Pharmacy & Pharmaceutical Sciences
ID Code:1170
Deposited By: Professor Paul McCarron
Deposited On:11 Apr 2017 14:42
Last Modified:11 Apr 2017 14:42

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