Oral efficacy of a diselenide compound loaded in nanostructured lipid carriers in a murine model of visceral leishmaniasis
Leishmaniasis urgently needs new oral treatments, as it is one of the most important neglected tropical diseases that affects people with poor resources. The drug discovery pipeline for oral administration currently discards entities with poor aqueous solubility and permeability (class IV compounds...
| Main Authors: | , , , , , , , , , , , |
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| Format: | info:eu-repo/semantics/article |
| Language: | English |
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2022
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| Online Access: | https://hdl.handle.net/10171/62944 |
| _version_ | 1793400395840618496 |
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| author | Etxebeste-Mitxeltorena, M. (Mikel) Moreno-Amatria, E. (Esther) Carvalheiro, M. (Manuela) Calvo-Bacaicoa, A. (Alba) Navarro-Blasco, I. (Iñigo) Gonzalez-Peñas, E. (Elena) Alvarez-Galindo, J.I. (José Ignacio) Plano-Amatriain, D. (Daniel) Irache, J.M. (Juan Manuel) Almeida, A.J. (Antonio J.) Sanmartin-Grijalba, C. (Carmen) Espuelas, S. (Socorro) |
| author_facet | Etxebeste-Mitxeltorena, M. (Mikel) Moreno-Amatria, E. (Esther) Carvalheiro, M. (Manuela) Calvo-Bacaicoa, A. (Alba) Navarro-Blasco, I. (Iñigo) Gonzalez-Peñas, E. (Elena) Alvarez-Galindo, J.I. (José Ignacio) Plano-Amatriain, D. (Daniel) Irache, J.M. (Juan Manuel) Almeida, A.J. (Antonio J.) Sanmartin-Grijalba, C. (Carmen) Espuelas, S. (Socorro) |
| author_sort | Etxebeste-Mitxeltorena, M. (Mikel) |
| collection | DSpace |
| description | Leishmaniasis urgently needs new oral treatments, as it is one of the most important neglected tropical diseases that affects people with poor resources. The drug discovery pipeline for oral administration currently discards entities with poor aqueous solubility and permeability (class IV compounds in the Biopharmaceutical Classification System, BCS) such as the diselenide 2m, a trypanothione reductase (TR) inhibitor. This work was assisted by glyceryl palmitostearate and diethylene glycol monoethyl ether-based nanostructured lipid carriers (NLC) to render 2m bioavailable and effective after its oral administration. The loading of 2m in NLC drastically enhanced its intestinal permeability and provided plasmatic levels higher than its effective concentration (IC50). In L. infantum-infected BALB/c mice, 2m-NLC reduced the parasite burden in the spleen, liver, and bone marrow by at least 95% after 5 doses, demonstrating similar efficacy as intravenous Fungizone. Overall, compound 2m and its formulation merit further investigation as an oral treatment for visceral leishmaniasis. |
| format | info:eu-repo/semantics/article |
| id | oai:dadun.unav.edu:10171-62944 |
| institution | Universidad de Navarra |
| language | English |
| publishDate | 2022 |
| record_format | dspace |
| spelling | oai:dadun.unav.edu:10171-629442022-02-19T02:03:50Z Oral efficacy of a diselenide compound loaded in nanostructured lipid carriers in a murine model of visceral leishmaniasis Etxebeste-Mitxeltorena, M. (Mikel) Moreno-Amatria, E. (Esther) Carvalheiro, M. (Manuela) Calvo-Bacaicoa, A. (Alba) Navarro-Blasco, I. (Iñigo) Gonzalez-Peñas, E. (Elena) Alvarez-Galindo, J.I. (José Ignacio) Plano-Amatriain, D. (Daniel) Irache, J.M. (Juan Manuel) Almeida, A.J. (Antonio J.) Sanmartin-Grijalba, C. (Carmen) Espuelas, S. (Socorro) Diselenide Nanostructured lipid carriers Visceral leishmanisis L. infantum Oral treatment Leishmaniasis urgently needs new oral treatments, as it is one of the most important neglected tropical diseases that affects people with poor resources. The drug discovery pipeline for oral administration currently discards entities with poor aqueous solubility and permeability (class IV compounds in the Biopharmaceutical Classification System, BCS) such as the diselenide 2m, a trypanothione reductase (TR) inhibitor. This work was assisted by glyceryl palmitostearate and diethylene glycol monoethyl ether-based nanostructured lipid carriers (NLC) to render 2m bioavailable and effective after its oral administration. The loading of 2m in NLC drastically enhanced its intestinal permeability and provided plasmatic levels higher than its effective concentration (IC50). In L. infantum-infected BALB/c mice, 2m-NLC reduced the parasite burden in the spleen, liver, and bone marrow by at least 95% after 5 doses, demonstrating similar efficacy as intravenous Fungizone. Overall, compound 2m and its formulation merit further investigation as an oral treatment for visceral leishmaniasis. 2022-02-18T11:03:23Z 2022-02-18T11:03:23Z 2021 info:eu-repo/semantics/article https://hdl.handle.net/10171/62944 en info:eu-repo/semantics/openAccess application/pdf |
| spellingShingle | Diselenide Nanostructured lipid carriers Visceral leishmanisis L. infantum Oral treatment Etxebeste-Mitxeltorena, M. (Mikel) Moreno-Amatria, E. (Esther) Carvalheiro, M. (Manuela) Calvo-Bacaicoa, A. (Alba) Navarro-Blasco, I. (Iñigo) Gonzalez-Peñas, E. (Elena) Alvarez-Galindo, J.I. (José Ignacio) Plano-Amatriain, D. (Daniel) Irache, J.M. (Juan Manuel) Almeida, A.J. (Antonio J.) Sanmartin-Grijalba, C. (Carmen) Espuelas, S. (Socorro) Oral efficacy of a diselenide compound loaded in nanostructured lipid carriers in a murine model of visceral leishmaniasis |
| title | Oral efficacy of a diselenide compound loaded in nanostructured lipid carriers in a murine model of visceral leishmaniasis |
| title_full | Oral efficacy of a diselenide compound loaded in nanostructured lipid carriers in a murine model of visceral leishmaniasis |
| title_fullStr | Oral efficacy of a diselenide compound loaded in nanostructured lipid carriers in a murine model of visceral leishmaniasis |
| title_full_unstemmed | Oral efficacy of a diselenide compound loaded in nanostructured lipid carriers in a murine model of visceral leishmaniasis |
| title_short | Oral efficacy of a diselenide compound loaded in nanostructured lipid carriers in a murine model of visceral leishmaniasis |
| title_sort | oral efficacy of a diselenide compound loaded in nanostructured lipid carriers in a murine model of visceral leishmaniasis |
| topic | Diselenide Nanostructured lipid carriers Visceral leishmanisis L. infantum Oral treatment |
| url | https://hdl.handle.net/10171/62944 |
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