Epidermal penetration and protoporphyrin IX formation of two different 5-aminolevulinic acid formulations in ex vivo human skin

Abstract

BackgroundPhotosensitizer formation and epidermal penetration depth represent basic predictors of drug efficacy in dermatological Photodynamic Therapy (PDT). Different drug formulations and application standards are used to perform PDT in clinical practice. MethodsThus, we developed a human ex vivo model suitable to explore drug permeation in human skin and compared in 10 patients the penetration of nanoemulsion formulation (BF-200 ALA) with that of a 20% ALA cream formulation frequently used in clinical practice. Protoporphyrin IX (PpIX) formation was assessed according to different durations of incubation with both preparations. ResultsBF-200 ALA led to more intense PpIX fluorescence than the 20% ALA cream formulation as assessed by fluorescence microscopy: after 12h of incubation, total measured fluorescence was at 101,995 fluorescence units with BF-200 ALA and 40,960 fluorescence units with 20% ALA cream, respectively. This could be reproduced using quantitative fluorimetric measurements in tissue lysates. After the clinically relevant incubation time of 3h the PpIX concentration induced by BF-200 ALA was more than three-fold higher than that induced by the 20% ALA formulation (7.1±5.5 and 1.9±1.8nmol/l, p<0.05, Mann–Whitney U-test) and four-fold higher after 12h (30.0±4.6 and 6.7±2.0nmol/l, p<0.01, Mann–Whitney U-test). ConclusionsIn spite of the 50% lower ALA content BF-200 ALA triggers significantly higher PpIX concentrations than the 20% ALA formulation, indicating that clinical efficacy with BF-200 ALA may be higher. Moreover, the ex vivo eyelid skin model may represent a useful tool to investigate drug permeation in human skin.