A vehicle for photodynamic therapy of skin cancer: influence of dimethylsulphoxide on 5-aminolevulinic acid in vitro cutaneous permeation and in vivo protoporphyrin IX accumulation determined by confocal microscopy
| Autor: | Juliana Maldonado Marchetti, Maria Vitória Lopes Badra Bentley, Antonio Claudio Tedesco, Fernanda Scarmato De Rosa, José Antônio Thomazini |
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| Rok vydání: | 2000 |
| Předmět: |
Skin Neoplasms
Skin Absorption medicine.medical_treatment Protoporphyrins Pharmaceutical Science Photodynamic therapy law.invention Mice chemistry.chemical_compound In vivo Confocal microscopy law medicine Animals Humans Dimethyl Sulfoxide Photosensitizer Chelation Skin Mice Hairless Microscopy Confocal Photosensitizing Agents Myristates integumentary system Protoporphyrin IX Aminolevulinic Acid Molecular biology Hairless Photochemotherapy Solubility chemistry Biochemistry Protoporphyrin Pharmaceutical Vehicles |
| Zdroj: | Journal of Controlled Release. 65:359-366 |
| ISSN: | 0168-3659 |
| Popis: | Topical application of 5-aminolevulinic acid (5-ALA) followed by light irradiation is a new concept of photodynamic therapy (PDT) of skin cancers. 5-ALA is a prodrug that can be converted by the heme biosynthetic pathway into protoporphyrin IX, an effective photosensitizer. In the present work we propose the enhancement of 5-ALA-induced protoporphyrin IX accumulation by dimethylsulphoxide (DMSO) and ethylenediamine-tetraacetic acid disodium salt (EDTA). The presence of 20% DMSO (w/w) in oil-in-water emulsions increased the in vitro permeation of 5-ALA through hairless mouse skin. In vivo studies demonstrated a significant increase in the amount of protoporphyrin IX extracted from healthy hairless mouse skin after 3 h treatment with an oil-in-water emulsion containing 10% 5-ALA (w/w), 3% EDTA (w/w) and 20% DMSO (w/w). By confocal scanning laser microscopy imaging, an observed increase in red fluorescence, at 476 nm excitation and emission detected longer than 590 nm, in skin that had received this treatment, was attributed to protoporphyrin IX accumulation. Although no effect of EDTA on short-term protoporphyrin IX accumulation in skin was detected, this chelator could protect 5-ALA from decomposition during prolonged topical administration. The results obtained indicate that association of 5-ALA, EDTA and 20% DMSO may enhance the delivery of 5-ALA to the skin in the topical PDT. |
| Databáze: | OpenAIRE |
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