In Vitro Metabolism of 5-ALA Esters Derivatives in Hairless Mice Skin Homogenate and in Vivo PpIX Accumulation Studies |
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Authors: | Fernanda Scarmato?De Rosa,Renata Fonseca Vianna?Lopez,José Ant?nio?Thomazine,Ant?nio Cláudio?Tedesco,Norbert?Lange,Maria Vitóoria Lopes Badra?Bentley author-information" > author-information__contact u-icon-before" > mailto:vbentley@usp.br" title=" vbentley@usp.br" itemprop=" email" data-track=" click" data-track-action=" Email author" data-track-label=" " >Email author |
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Affiliation: | (1) Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences of Ribeiro Preto, University of So Paulo, Av. Café s/n, 14040-903, Ribeiro Preto, São Paulo, 14049-900 Ribeirão Preto, Brazil;(2) Department of Surgery and Anatomy, Faculty of Medicine of Ribeiro Preto, University So Paulo, Brazil;(3) Department of Chemistry, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, University São Paulo, 14040-901 Ribeirão Preto, Brazil;(4) School of Pharmacy, University of Lausanne, CH-1211 Lausanne, Switzerland |
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Abstract: | No HeadingPurpose. In topical photodynamic therapy, 5-ALA and its esters are enzymatically converted in the endogenous photosensitizing compounds such as, for example, protoporphyrin IX (PpIX). In order to elucidate in more detail their enzymatic fate, we have determined in vitro the enzymatic degradation of methyl, butyl, hexyl, and octyl-5-ALA ester derivatives in skin homogenate. Furthermore, in vivo porphyrin accumulation was measured in healthy hairless mice skins.Methods. Hairless mouse skins were homogenized in isotonic phosphate buffer pH 7.4. 5-ALA esters were added, and aliquots were colleted for HPLC-fluorimetric determinations of remaining content of 5-ALA esters. Furthermore, oil-in-water emulsions containing esters were topically applied to mice skin for 6 h, and the amount of accumulated PpIX in the treated areas was determined by quantitative extraction and confocal fluorescence microscopy.Results. The enzymatic degradation of esters follows pseudo first-order kinetics. The octyl ester had the largest rate constant for enzymatic degradation, followed by hexyl-, butyl-, and methyl-ALA. The long-chained 5-ALA esters, butyl-, hexyl-, and octyl ester, induced significantly more porphyrins than 5-ALA and 5-ALA methyl ester as shown by confocal microscopy and quantitative extraction studies.Conclusions. 5-ALA derivatives differ widely with respect to their enzymatic degradation. The presence of alkyl chains in 5-ALA esters significantly influences the in vitro enzymatic metabolism and the in vivo PpIX formation in healthy hairless mice skins. |
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Keywords: | 5-ALA ester derivatives 5-aminolevulinic acid photodynamic therapy protoporphyrin IX skin metabolism |
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