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Abstract:

Background The optimal vehicle to ensure adequate penetration of 5-aminolaevulinic acid (ALA) for its use in photodynamic therapy (PDT) of skin lesions has not been determined. Objectives We aimed to study the effects of ALA in various vehicle formulations [saline lotion with and without dimethylsulphoxide (DMSO), cream, liposomes and vaseline] after topical application in a murine subcutaneous adenocarcinoma model. Methods: The effect of DMSO on porphyrin synthesis and ALA penetration through the skin was studied by measuring the uptake of 14C label from ALA, ALA and porphobilinogen accumulation, and some haem enzyme activities. The tissue distribution and kinetics of porphyrin synthesis after topical application of ALA entrapped in large multilamellar liposomes was also determined. Results ALA in saline lotion, alone or with 10% DMSO, proved to be the most efficient vehicle for tumour porphyrin accumulation (mean ± SD 1.75 ± 0.25 and 2.09 ± 0.39 μg g-1, respectively), whereas cream and liposomes induced lower levels and identical porphyrin accumulation (0.60 μg g-1). Using ALA + DMSO saline lotion, a higher porphyrin accumulation was found in skin overlying the tumour tissue and in the first 2 mm of tumour, probably due to increased ALA penetration, or greater interconversion to porphyrins, or greater retention of ALA and/or porphyrins. Conclusions These findings reinforce the importance of the vehicle in topical ALA-based PDT, and explain the mechanism of action of DMSO in enhancing protoporphyrin IX biosynthesis in superficial lesions.

Registro:

Documento: Artículo
Título:The influence of the vehicle on the synthesis of porphyrins after topical application of 5-aminolaevulinic acid. Implications in cutaneous photodynamic sensitization
Autor:Casas, A.; Fukuda, H.; Di Venosa, G.; Del C.Batlle, A.M.
Filiación:Ctro. de Invest. Sobre Porfirinas Y Porfirias (CIPYP) FCEyN (University of Buenos Aires and CONICET), Ciudad Universitaria, Pabellón II, 2do piso, (1428) Capital Federal, Argentina
Viamonte 1881 10A, 1056 Buenos Aires, Argentina
Palabras clave:5-Aminolaevulinic acid; Dimethylsulphoxide; Liposomes; Photodynamic therapy; Porphyrins; Topical application; aminolevulinic acid; dimethyl sulfoxide; drug vehicle; enzyme; liposome; petrolatum; porphobilinogen; porphyrin; animal experiment; animal model; animal tissue; article; controlled study; cream; drug distribution; drug effect; drug formulation; drug mechanism; drug penetration; lotion; male; mouse; nonhuman; photodynamic therapy; photosensitization; priority journal; skin cancer; Adenocarcinoma; Administration, Topical; Aminolevulinic Acid; Animals; Carbon Radioisotopes; Dimethyl Sulfoxide; Drug Carriers; Isotonic Solutions; Liposomes; Male; Mice; Mice, Inbred BALB C; Photochemotherapy; Photosensitizing Agents; Porphyrins; Skin; Skin Neoplasms; Sodium Chloride; Solvents
Año:2000
Volumen:143
Número:3
Página de inicio:564
Página de fin:572
DOI: http://dx.doi.org/10.1046/j.1365-2133.2000.03711.x
Título revista:British Journal of Dermatology
Título revista abreviado:Br. J. Dermatol.
ISSN:00070963
CODEN:BJDEA
CAS:Aminolevulinic Acid, 106-60-5; Carbon Radioisotopes; Dimethyl Sulfoxide, 67-68-5; Drug Carriers; Isotonic Solutions; Liposomes; Photosensitizing Agents; Porphyrins; Sodium Chloride, 7647-14-5; Solvents
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00070963_v143_n3_p564_Casas

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Citas:

---------- APA ----------
Casas, A., Fukuda, H., Di Venosa, G. & Del C.Batlle, A.M. (2000) . The influence of the vehicle on the synthesis of porphyrins after topical application of 5-aminolaevulinic acid. Implications in cutaneous photodynamic sensitization. British Journal of Dermatology, 143(3), 564-572.
http://dx.doi.org/10.1046/j.1365-2133.2000.03711.x
---------- CHICAGO ----------
Casas, A., Fukuda, H., Di Venosa, G., Del C.Batlle, A.M. "The influence of the vehicle on the synthesis of porphyrins after topical application of 5-aminolaevulinic acid. Implications in cutaneous photodynamic sensitization" . British Journal of Dermatology 143, no. 3 (2000) : 564-572.
http://dx.doi.org/10.1046/j.1365-2133.2000.03711.x
---------- MLA ----------
Casas, A., Fukuda, H., Di Venosa, G., Del C.Batlle, A.M. "The influence of the vehicle on the synthesis of porphyrins after topical application of 5-aminolaevulinic acid. Implications in cutaneous photodynamic sensitization" . British Journal of Dermatology, vol. 143, no. 3, 2000, pp. 564-572.
http://dx.doi.org/10.1046/j.1365-2133.2000.03711.x
---------- VANCOUVER ----------
Casas, A., Fukuda, H., Di Venosa, G., Del C.Batlle, A.M. The influence of the vehicle on the synthesis of porphyrins after topical application of 5-aminolaevulinic acid. Implications in cutaneous photodynamic sensitization. Br. J. Dermatol. 2000;143(3):564-572.
http://dx.doi.org/10.1046/j.1365-2133.2000.03711.x