Evaluation of skin permeation and retention of topical dapsone in murine cutaneous leishmaniasis lesions
The oral administration of dapsone (DAP) for the treatment of cutaneous leishmaniasis (CL) is effective, although serious hematological side effects limit its use. In this study, we evaluated this drug for the topical treatment of CL. As efficacy depends on potency and skin penetration, we first det...
| Main Authors: | , , , , , , , |
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| Format: | info:eu-repo/semantics/article |
| Language: | English |
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2019
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| Online Access: | https://hdl.handle.net/10171/58480 |
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| author | Espuelas, S. (Socorro) Irache, J.M. (Juan Manuel) Sanmartin-Grijalba, C. (Carmen) Gonzalez-Peñas, E. (Elena) Navarro-Blasco, I. (Iñigo) Schwartz, J. (Juana) Calvo-Bacaicoa, A. (Alba) Moreno-Amatria, E. (Esther) |
| author_facet | Espuelas, S. (Socorro) Irache, J.M. (Juan Manuel) Sanmartin-Grijalba, C. (Carmen) Gonzalez-Peñas, E. (Elena) Navarro-Blasco, I. (Iñigo) Schwartz, J. (Juana) Calvo-Bacaicoa, A. (Alba) Moreno-Amatria, E. (Esther) |
| author_sort | Espuelas, S. (Socorro) |
| collection | DSpace |
| description | The oral administration of dapsone (DAP) for the treatment of cutaneous leishmaniasis (CL) is effective, although serious hematological side effects limit its use. In this study, we evaluated this drug for the topical treatment of CL. As efficacy depends on potency and skin penetration, we first determined its antileishmanial activity (IC50 = 100 ¿M) and selectivity index in vitro against Leishmania major-infected macrophages. In order to evaluate the skin penetration ex vivo, we compared an O/W cream containing DAP that had been micronized with a pluronic lecithin emulgel, in which the drug was solubilized with diethylene glycol monoethyl ether. For both formulations we obtained similar low flux values that increased when the stratum corneum and the epidermis were removed. In vivo efficacy studies performed on L. major-infected BALB/c mice revealed that treatment not only failed to cure the lesions but made their evolution and appearance worse. High plasma drug levels were detected and were concomitant with anemia and iron accumulation in the spleen. This side effect was correlated with a reduction of parasite burden in this organ. Our results evidenced that DAP in these formulations does not have an adequate safety index for use in the topical therapy of CL. |
| format | info:eu-repo/semantics/article |
| id | oai:dadun.unav.edu:10171-58480 |
| institution | Universidad de Navarra |
| language | English |
| publishDate | 2019 |
| record_format | dspace |
| spelling | oai:dadun.unav.edu:10171-584802020-03-04T03:56:10Z Evaluation of skin permeation and retention of topical dapsone in murine cutaneous leishmaniasis lesions Espuelas, S. (Socorro) Irache, J.M. (Juan Manuel) Sanmartin-Grijalba, C. (Carmen) Gonzalez-Peñas, E. (Elena) Navarro-Blasco, I. (Iñigo) Schwartz, J. (Juana) Calvo-Bacaicoa, A. (Alba) Moreno-Amatria, E. (Esther) Dapsone Topical treatment Cutaneous leishmaniasis Pluronic lecithin emulgel Iron The oral administration of dapsone (DAP) for the treatment of cutaneous leishmaniasis (CL) is effective, although serious hematological side effects limit its use. In this study, we evaluated this drug for the topical treatment of CL. As efficacy depends on potency and skin penetration, we first determined its antileishmanial activity (IC50 = 100 ¿M) and selectivity index in vitro against Leishmania major-infected macrophages. In order to evaluate the skin penetration ex vivo, we compared an O/W cream containing DAP that had been micronized with a pluronic lecithin emulgel, in which the drug was solubilized with diethylene glycol monoethyl ether. For both formulations we obtained similar low flux values that increased when the stratum corneum and the epidermis were removed. In vivo efficacy studies performed on L. major-infected BALB/c mice revealed that treatment not only failed to cure the lesions but made their evolution and appearance worse. High plasma drug levels were detected and were concomitant with anemia and iron accumulation in the spleen. This side effect was correlated with a reduction of parasite burden in this organ. Our results evidenced that DAP in these formulations does not have an adequate safety index for use in the topical therapy of CL. 2019-11-20T12:41:55Z 2019-11-20T12:41:55Z 2019 info:eu-repo/semantics/article https://hdl.handle.net/10171/58480 en info:eu-repo/semantics/openAccess application/pdf |
| spellingShingle | Dapsone Topical treatment Cutaneous leishmaniasis Pluronic lecithin emulgel Iron Espuelas, S. (Socorro) Irache, J.M. (Juan Manuel) Sanmartin-Grijalba, C. (Carmen) Gonzalez-Peñas, E. (Elena) Navarro-Blasco, I. (Iñigo) Schwartz, J. (Juana) Calvo-Bacaicoa, A. (Alba) Moreno-Amatria, E. (Esther) Evaluation of skin permeation and retention of topical dapsone in murine cutaneous leishmaniasis lesions |
| title | Evaluation of skin permeation and retention of topical dapsone in murine cutaneous leishmaniasis lesions |
| title_full | Evaluation of skin permeation and retention of topical dapsone in murine cutaneous leishmaniasis lesions |
| title_fullStr | Evaluation of skin permeation and retention of topical dapsone in murine cutaneous leishmaniasis lesions |
| title_full_unstemmed | Evaluation of skin permeation and retention of topical dapsone in murine cutaneous leishmaniasis lesions |
| title_short | Evaluation of skin permeation and retention of topical dapsone in murine cutaneous leishmaniasis lesions |
| title_sort | evaluation of skin permeation and retention of topical dapsone in murine cutaneous leishmaniasis lesions |
| topic | Dapsone Topical treatment Cutaneous leishmaniasis Pluronic lecithin emulgel Iron |
| url | https://hdl.handle.net/10171/58480 |
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