The influence of the vehicle on the synthesis of porphyrins after topical application of 5-aminolaevulinic acid. Implications in cutaneous photodynamic sensitization
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 dimethylsul...
Guardado en:
| Autores principales: | , , , |
|---|---|
| Formato: | JOUR |
| Materias: | |
| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_00070963_v143_n3_p564_Casas |
| Aporte de: |
| id |
todo:paper_00070963_v143_n3_p564_Casas |
|---|---|
| record_format |
dspace |
| spelling |
todo:paper_00070963_v143_n3_p564_Casas2023-10-03T14:05:29Z The influence of the vehicle on the synthesis of porphyrins after topical application of 5-aminolaevulinic acid. Implications in cutaneous photodynamic sensitization Casas, A. Fukuda, H. Di Venosa, G. Del C.Batlle, A.M. 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 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. Fil:Casas, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Fukuda, H. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Di Venosa, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Del C.Batlle, A.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00070963_v143_n3_p564_Casas |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 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 |
| topic_facet |
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 |
| description |
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. |
| format |
JOUR |
| author |
Casas, A. Fukuda, H. Di Venosa, G. Del C.Batlle, A.M. |
| author_facet |
Casas, A. Fukuda, H. Di Venosa, G. Del C.Batlle, A.M. |
| author_sort |
Casas, A. |
| title |
The influence of the vehicle on the synthesis of porphyrins after topical application of 5-aminolaevulinic acid. Implications in cutaneous photodynamic sensitization |
| title_short |
The influence of the vehicle on the synthesis of porphyrins after topical application of 5-aminolaevulinic acid. Implications in cutaneous photodynamic sensitization |
| title_full |
The influence of the vehicle on the synthesis of porphyrins after topical application of 5-aminolaevulinic acid. Implications in cutaneous photodynamic sensitization |
| title_fullStr |
The influence of the vehicle on the synthesis of porphyrins after topical application of 5-aminolaevulinic acid. Implications in cutaneous photodynamic sensitization |
| title_full_unstemmed |
The influence of the vehicle on the synthesis of porphyrins after topical application of 5-aminolaevulinic acid. Implications in cutaneous photodynamic sensitization |
| title_sort |
influence of the vehicle on the synthesis of porphyrins after topical application of 5-aminolaevulinic acid. implications in cutaneous photodynamic sensitization |
| url |
http://hdl.handle.net/20.500.12110/paper_00070963_v143_n3_p564_Casas |
| work_keys_str_mv |
AT casasa theinfluenceofthevehicleonthesynthesisofporphyrinsaftertopicalapplicationof5aminolaevulinicacidimplicationsincutaneousphotodynamicsensitization AT fukudah theinfluenceofthevehicleonthesynthesisofporphyrinsaftertopicalapplicationof5aminolaevulinicacidimplicationsincutaneousphotodynamicsensitization AT divenosag theinfluenceofthevehicleonthesynthesisofporphyrinsaftertopicalapplicationof5aminolaevulinicacidimplicationsincutaneousphotodynamicsensitization AT delcbatlleam theinfluenceofthevehicleonthesynthesisofporphyrinsaftertopicalapplicationof5aminolaevulinicacidimplicationsincutaneousphotodynamicsensitization AT casasa influenceofthevehicleonthesynthesisofporphyrinsaftertopicalapplicationof5aminolaevulinicacidimplicationsincutaneousphotodynamicsensitization AT fukudah influenceofthevehicleonthesynthesisofporphyrinsaftertopicalapplicationof5aminolaevulinicacidimplicationsincutaneousphotodynamicsensitization AT divenosag influenceofthevehicleonthesynthesisofporphyrinsaftertopicalapplicationof5aminolaevulinicacidimplicationsincutaneousphotodynamicsensitization AT delcbatlleam influenceofthevehicleonthesynthesisofporphyrinsaftertopicalapplicationof5aminolaevulinicacidimplicationsincutaneousphotodynamicsensitization |
| _version_ |
1807323694030127104 |