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Aminolevulinic acid derivatives and liposome delivery as strategies for improving 5-aminolevulinic acid-mediated photodynamic therapy.

Authors
  • Casas, Adriana1
  • Batlle, Alcira
  • 1 Centro de Investigaciones sobre Porfirinas y Porfirias, CONICET and Hospital de Clínicas José de San Martín, University of Buenos Aires, Córdoba 2351 1er subsuelo, Ciudad de Buenos Aires, Argentina. [email protected] , (Argentina)
Type
Published Article
Journal
Current medicinal chemistry
Publication Date
Jan 01, 2006
Volume
13
Issue
10
Pages
1157–1168
Identifiers
PMID: 16719777
Source
Medline
License
Unknown

Abstract

Photodynamic Therapy employing 5-aminolevulinic acid (ALA) as a precursor of the photosensitizer Protoporphyrin IX has become a promising approach to treat superficial cancers. However, the hydrophilic nature of the ALA molecule somewhat limits the penetration through the skin as well as all cell membranes. Different attempts are currently under investigation to enhance ALA penetration, such as the development of new synthetic and more lipophilic molecules derived from ALA and the incorporation of ALA into lipophilic vehicles such as liposomes. Among the new synthesized molecules, we can find ALA esters, ALA aminoacid derivatives and ALA dendrimers. In general, there is consensus that the promising results obtained in vitro with ALA esters cannot be reproduced in vivo. However, ALA methyl ester (1) has been widely used for treatment of skin malignancies and ALA hexyl ester (15) proved to be more powerful than ALA in bladder imaging. ALA aminoacid derivatives have been designed to use specific cellular aminopeptidases to targeting tumors, and it was shown that they can be metabolized to ALA with some specificity.

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