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• W2001749797 abstract "Summary Background Photodynamic therapy (PDT) using topical application of 5‐aminolaevulinic acid (ALA) has been widely reported for the treatment of a variety of neoplastic and non‐neoplastic cutaneous diseases. Although different formulations containing variable amounts of ALA have been applied in PDT, the dose–response relationships between transdermal ALA delivery and cutaneous protoporphyrin IX (PpIX) accumulation have not been studied. Objectives and methods The objectives of this study were to investigate the effect of permeability barrier function, ALA concentration and formulation on the in vitro penetration of ALA through nude mouse skin and cutaneous PpIX formation at 2 h following a 2‐h application of ALA to nude mouse skin in vivo, and to delineate the relationships in between. Results Results demonstrated that variations in barrier integrity, in addition to ALA concentration, profoundly influenced ALA delivery to generate PpIX. Saturable correlations were found to exist between PpIX concentrations in both the epidermis and dermis in vivo and its transdermal flux in vitro, and the relationships were well described by the Emax model. The established correlations based on pure aqueous solutions were applicable to different formulations containing hydroxypropylmethylcellulose as the gelling agent and ethylenediamine tetraacetic acid as the iron chelator. Moreover, incorporation of desferrioxamine, another iron chelator, in the formulation prolonged cutaneous PpIX accumulation in the skin in comparison with 3% ALA aqueous solution, but the peak PpIX levels were not increased. Application of a liposomal formulation resulted in similar prolongation in ALA‐induced PpIX accumulation, as well as better epidermal targeting. Conclusions Knowledge of the dose–response relationships and the effect of formulation is important for designing optimal formulations and treatment schedules for topical ALA‐PDT." @default.
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• W2001749797 date "2002-05-01" @default.
• W2001749797 modified "2023-09-25" @default.
• W2001749797 title "In vitro/in vivo correlations between transdermal delivery of 5-aminolaevulinic acid and cutaneous protoporphyrin IX accumulation and effect of formulation" @default.
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• W2001749797 doi "https://doi.org/10.1046/j.1365-2133.2002.04715.x" @default.
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