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...
| Autores: | , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/62944 |
| Acceso en línea: | https://hdl.handle.net/10171/62944 |
| Access Level: | acceso abierto |
| Palabra clave: | Diselenide Nanostructured lipid carriers Visceral leishmanisis L. infantum Oral treatment |
| id |
ES_0d16e8ce1379fc751d182dfd487ad481 |
|---|---|
| oai_identifier_str |
oai:dadun.unav.edu:10171/62944 |
| network_acronym_str |
ES |
| network_name_str |
España |
| repository_id_str |
|
| spelling |
Oral efficacy of a diselenide compound loaded in nanostructured lipid carriers in a murine model of visceral leishmaniasisEtxebeste-Mitxeltorena, M. (Mikel)|||/items/ed41b569-69ef-41f9-805b-e0b9b1e49191Moreno-Amatria, E. (Esther)|||/items/9dcce7d3-851e-4ffb-9cd0-2f07c8599f4fCarvalheiro, M. (Manuela)|||/items/84f57a69-92e6-41c5-a3f8-e6e4af08a060Calvo-Bacaicoa, A. (Alba)|||/items/8557046e-51a2-45a9-b289-9b6e0b1648d3Navarro-Blasco, I. (Iñigo)|||/items/733b109b-1074-49e9-8952-70ec6928cc54Gonzalez-Peñas, E. (Elena)|||/items/0e4b9ed7-4224-4664-a4f1-c6403a8c833fAlvarez-Galindo, J.I. (José Ignacio)|||/items/c88ef755-513c-4ff3-bbff-44aadbf32204Plano-Amatriain, D. (Daniel)|||/items/238881e4-7d5e-4598-924d-4392e3b7e02eIrache-Garreta, J.M. (Juan Manuel)|||/items/c7cbbe9e-faeb-47e1-b7e8-2d956ca50173Almeida, A.J. (Antonio J.)|||/items/bc31603c-5436-4a19-99ab-3ec476e07f2fSanmartin-Grijalba, C. (Carmen)|||/items/d36bd105-ab64-427d-9745-5812cf5e7af7Espuelas, S. (Socorro)|||/items/b57c05de-0bc4-4fcf-ae1e-c9b2fb92964cDiselenideNanostructured lipid carriersVisceral leishmanisisL. infantumOral treatmentLeishmaniasis 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.Dadun. Depósito Académico Digital Universidad de Navarra20222022-02-1820212021-01-0120212021-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/62944reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/629442026-06-21T12:47:57Z |
| dc.title.none.fl_str_mv |
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 |
| spellingShingle |
Oral efficacy of a diselenide compound loaded in nanostructured lipid carriers in a murine model of visceral leishmaniasis Etxebeste-Mitxeltorena, M. (Mikel)|||/items/ed41b569-69ef-41f9-805b-e0b9b1e49191 Diselenide Nanostructured lipid carriers Visceral leishmanisis L. infantum Oral treatment |
| title_short |
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_sort |
Oral efficacy of a diselenide compound loaded in nanostructured lipid carriers in a murine model of visceral leishmaniasis |
| dc.creator.none.fl_str_mv |
Etxebeste-Mitxeltorena, M. (Mikel)|||/items/ed41b569-69ef-41f9-805b-e0b9b1e49191 Moreno-Amatria, E. (Esther)|||/items/9dcce7d3-851e-4ffb-9cd0-2f07c8599f4f Carvalheiro, M. (Manuela)|||/items/84f57a69-92e6-41c5-a3f8-e6e4af08a060 Calvo-Bacaicoa, A. (Alba)|||/items/8557046e-51a2-45a9-b289-9b6e0b1648d3 Navarro-Blasco, I. (Iñigo)|||/items/733b109b-1074-49e9-8952-70ec6928cc54 Gonzalez-Peñas, E. (Elena)|||/items/0e4b9ed7-4224-4664-a4f1-c6403a8c833f Alvarez-Galindo, J.I. (José Ignacio)|||/items/c88ef755-513c-4ff3-bbff-44aadbf32204 Plano-Amatriain, D. (Daniel)|||/items/238881e4-7d5e-4598-924d-4392e3b7e02e Irache-Garreta, J.M. (Juan Manuel)|||/items/c7cbbe9e-faeb-47e1-b7e8-2d956ca50173 Almeida, A.J. (Antonio J.)|||/items/bc31603c-5436-4a19-99ab-3ec476e07f2f Sanmartin-Grijalba, C. (Carmen)|||/items/d36bd105-ab64-427d-9745-5812cf5e7af7 Espuelas, S. (Socorro)|||/items/b57c05de-0bc4-4fcf-ae1e-c9b2fb92964c |
| author |
Etxebeste-Mitxeltorena, M. (Mikel)|||/items/ed41b569-69ef-41f9-805b-e0b9b1e49191 |
| author_facet |
Etxebeste-Mitxeltorena, M. (Mikel)|||/items/ed41b569-69ef-41f9-805b-e0b9b1e49191 Moreno-Amatria, E. (Esther)|||/items/9dcce7d3-851e-4ffb-9cd0-2f07c8599f4f Carvalheiro, M. (Manuela)|||/items/84f57a69-92e6-41c5-a3f8-e6e4af08a060 Calvo-Bacaicoa, A. (Alba)|||/items/8557046e-51a2-45a9-b289-9b6e0b1648d3 Navarro-Blasco, I. (Iñigo)|||/items/733b109b-1074-49e9-8952-70ec6928cc54 Gonzalez-Peñas, E. (Elena)|||/items/0e4b9ed7-4224-4664-a4f1-c6403a8c833f Alvarez-Galindo, J.I. (José Ignacio)|||/items/c88ef755-513c-4ff3-bbff-44aadbf32204 Plano-Amatriain, D. (Daniel)|||/items/238881e4-7d5e-4598-924d-4392e3b7e02e Irache-Garreta, J.M. (Juan Manuel)|||/items/c7cbbe9e-faeb-47e1-b7e8-2d956ca50173 Almeida, A.J. (Antonio J.)|||/items/bc31603c-5436-4a19-99ab-3ec476e07f2f Sanmartin-Grijalba, C. (Carmen)|||/items/d36bd105-ab64-427d-9745-5812cf5e7af7 Espuelas, S. (Socorro)|||/items/b57c05de-0bc4-4fcf-ae1e-c9b2fb92964c |
| author_role |
author |
| author2 |
Moreno-Amatria, E. (Esther)|||/items/9dcce7d3-851e-4ffb-9cd0-2f07c8599f4f Carvalheiro, M. (Manuela)|||/items/84f57a69-92e6-41c5-a3f8-e6e4af08a060 Calvo-Bacaicoa, A. (Alba)|||/items/8557046e-51a2-45a9-b289-9b6e0b1648d3 Navarro-Blasco, I. (Iñigo)|||/items/733b109b-1074-49e9-8952-70ec6928cc54 Gonzalez-Peñas, E. (Elena)|||/items/0e4b9ed7-4224-4664-a4f1-c6403a8c833f Alvarez-Galindo, J.I. (José Ignacio)|||/items/c88ef755-513c-4ff3-bbff-44aadbf32204 Plano-Amatriain, D. (Daniel)|||/items/238881e4-7d5e-4598-924d-4392e3b7e02e Irache-Garreta, J.M. (Juan Manuel)|||/items/c7cbbe9e-faeb-47e1-b7e8-2d956ca50173 Almeida, A.J. (Antonio J.)|||/items/bc31603c-5436-4a19-99ab-3ec476e07f2f Sanmartin-Grijalba, C. (Carmen)|||/items/d36bd105-ab64-427d-9745-5812cf5e7af7 Espuelas, S. (Socorro)|||/items/b57c05de-0bc4-4fcf-ae1e-c9b2fb92964c |
| author2_role |
author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Dadun. Depósito Académico Digital Universidad de Navarra |
| dc.subject.none.fl_str_mv |
Diselenide Nanostructured lipid carriers Visceral leishmanisis L. infantum Oral treatment |
| topic |
Diselenide Nanostructured lipid carriers Visceral leishmanisis L. infantum Oral treatment |
| 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. |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021 2021-01-01 2021 2021-01-01 2022 2022-02-18 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/10171/62944 |
| url |
https://hdl.handle.net/10171/62944 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.source.none.fl_str_mv |
reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra |
| instname_str |
Universidad de Navarra |
| reponame_str |
Dadun. Depósito Académico Digital de la Universidad de Navarra |
| collection |
Dadun. Depósito Académico Digital de la Universidad de Navarra |
| repository.name.fl_str_mv |
|
| repository.mail.fl_str_mv |
|
| _version_ |
1869403320276221952 |
| score |
15,300719 |