Abstract
Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) is the most widely used form of PDT in clinical practice. Topical application of ALA leads to overproduction of the endogenous photosensitizer protoporphyrin IX (PpIX). ALA-PDT is efficient treatment of superficial skin lesions, but not for thicker lesions. The main reason for this is suboptimal penetration of ALA molecules through cellular membranes and through stratum corneum of intact skin. Different approaches (formulations, mechanical and physical penetration enhancers, ALA derivatives) are currently used to increase the penetration. The content and distribution of ALA intracellularly and in tissues is difficult to measure, but PpIX content, on a relative scale, can be easily measured by fluorimetric assays.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Peng, Q., Warloe, T., Berg, K., Moan, J., Kongshaug, M., Giercksky, K. E., and Nesland, J. M. (1997) 5-Aminolevulinic acid-based photodynamic therapy. Clinical research and future challenges. Cancer, 79, 2282–2308.
Morton, C. A., McKenna, K. E., and Rhodes, L. E. (2008) Guidelines for topical photodynamic therapy: update. Br J Dermatol, 159, 1245–1266.
Donnelly, R. F., McCarron, P. A., and Woolfson, A. D. (2005) Drug delivery of aminolevulinic acid from topical formulations intended for photodynamic therapy. Photochem Photobiol, 81, 750–767.
Morrow, D. I., Garland, M. J., McCarron, P. A., Woolfson, A. D., and Donnelly, R. F. (2007) Innovative drug delivery strategies for topical photodynamic therapy using porphyrin precursors. J Environ Pathol Toxicol Oncol, 26, 105–116.
Donnelly, R. F., McCarron, P. A., Morrow, D. I., Sibani, S. A., and Woolfson, A. D. (2008) Photosensitiser delivery for photodynamic therapy. Part 1: topical carrier platforms. Expert Opin Drug Deliv, 5, 757–766.
Hua, Z., Gibson, S. L., Foster, T. H., and Hilf, R. (1995) Effectiveness of delta-aminolevulinic acid-induced protoporphyrin as a photosensitizer for photodynamic therapy in vivo. Cancer Res, 55, 1723–1731.
Luksiene, Z., Eggen, I., Moan, J., Nesland, J. M., and Peng, Q. (2001) Evaluation of protoporphyrin IX production, phototoxicity and cell death pathway induced by hexylester of 5-aminolevulinic acid in Reh and HPB-ALL cells. Cancer Lett, 169, 33–39.
Sato, N., Moore, B. W., Keevey, S., Drazba, J. A., Hasan, T., and Maytin, E. V. (2007) Vitamin D enhances ALA-induced protoporphyrin IX production and photodynamic cell death in 3-D organotypic cultures of keratinocytes. J Invest Dermatol, 127, 925–934.
Gaullier, J. M., Berg, K., Peng, Q., Anholt, H., Selbo, P. K., Ma, L. W., and Moan, J. (1997) Use of 5-aminolevulinic acid esters to improve photodynamic therapy on cells in culture. Cancer Res, 57, 1481–1486.
Moan, J., Ma, L. W., Juzeniene, A., Iani, V., Juzenas, P., Apricena, F., and Peng, Q. (2003) Pharmacology of protoporphyrin IX in nude mice after application of ALA and ALA esters. Int J Cancer, 103, 132–135.
Margalit, R., Shaklai, N., and Cohen, S. (1983) Fluorimetric studies on the dimerization equilibrium of protoporphyrin IX and its haemato derivative. Biochem J, 209, 547–552.
Moan, J. (1984) The photochemical yield of singlet oxygen from porphyrins in different states of aggregation. Photochem Photobiol, 39, 445–449.
Juzenas, P., Juzeniene, A., Stakland, S., Iani, V., and Moan, J. (2002) Photosensitizing effect of protoporphyrin IX in pigmented melanoma of mice. Biochem Biophys Res Commun, 297, 468–472.
Hanania, J. and Malik, Z. (1992) The effect of EDTA and serum on endogenous porphyrin accumulation and photodynamic sensitization of human K562 leukemic cells. Cancer Lett, 65, 127–131.
Iinuma, S., Farshi, S. S., Ortel, B., and Hasan, T. (1994) A mechanistic study of cellular photodestruction with 5-aminolaevulinic acid-induced porphyrin. Br J Cancer, 70, 21–28.
Gomer, C. J., Jester, J. V., Razum, N. J., Szirth, B. C., and Murphree, A. L. (1985) Photodynamic therapy of intraocular tumors: examination of hematoporphyrin derivative distribution and long-term damage in rabbit ocular tissue. Cancer Res, 45, 3718–3725.
Acknowledgements
We appreciate financial support from the Norwegian Cancer Society (Kreftforeningen). As well P. Juzenas would like to acknowledge researcher grant received from the Research Council of Norway (Forskningsrådet). The authors also thank Vladimir Iani and Dr. Li-Wei Ma for technical assistance, reading the manuscript and giving valuable comments and suggestions.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Juzeniene, A., Juzenas, P., Moan, J. (2010). Application of 5-Aminolevulinic Acid and Its Derivatives for Photodynamic Therapy In Vitro and In Vivo. In: Gomer, C. (eds) Photodynamic Therapy. Methods in Molecular Biology, vol 635. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-697-9_7
Download citation
DOI: https://doi.org/10.1007/978-1-60761-697-9_7
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-60761-696-2
Online ISBN: 978-1-60761-697-9
eBook Packages: Springer Protocols