Chitosan derivatives as nanocarriers for hLDHA inhibitors delivery to hepatic cells
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10362/146554 |
Resumo: | Authors wish to thank the Centro de Instrumentación Científico-Técnica (CICT) of the University of Jaén, Spain, for partial financial support. A.A.-A. is grateful for the postdoctoral fellowship from Fundación Alfonso Martín Escudero. Authors acknowledge the use of the National Facility ELECMI ICTS, node “Laboratorio de Microscopias Avanzadas” at Universidad de Zaragoza. This research has also partially been supported by the Spanish Ministerio de Ciencia, Innovación y Universidades (grant RTI2018-098560-B-C22) and by the Andalusian Consejería de Economía y Conocimiento (FEDER program 2014-2020: grant number 1380682). Publisher Copyright: © 2022 The Author(s) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Chitosan derivatives as nanocarriers for hLDHA inhibitors delivery to hepatic cellsA selective strategy for targeting primary hyperoxaluria diseasesChitosanHepatocytes drug deliveryhLDHA inhibitorsPolymeric micellesPrimary hyperoxaluriaRedox-sensitivePharmaceutical ScienceSDG 3 - Good Health and Well-beingAuthors wish to thank the Centro de Instrumentación Científico-Técnica (CICT) of the University of Jaén, Spain, for partial financial support. A.A.-A. is grateful for the postdoctoral fellowship from Fundación Alfonso Martín Escudero. Authors acknowledge the use of the National Facility ELECMI ICTS, node “Laboratorio de Microscopias Avanzadas” at Universidad de Zaragoza. This research has also partially been supported by the Spanish Ministerio de Ciencia, Innovación y Universidades (grant RTI2018-098560-B-C22) and by the Andalusian Consejería de Economía y Conocimiento (FEDER program 2014-2020: grant number 1380682). Publisher Copyright: © 2022 The Author(s)Primary hyperoxalurias (PHs) are a group of inherited alterations of the hepatic glyoxylate metabolism that result in an excess of oxalate production by the oxidation of glyoxylate by the human lactate dehydrogenase A enzyme (hLDHA). The selective liver inhibition of this enzyme is one of the therapeutic strategies followed in the treatment of this disease. Even though several efforts have been recently performed using gene silencing by the RNA interference approach, small-molecule inhibitors that selectively reach hepatocytes are preferred since they present the advantages of a lower production cost and better pharmacological properties. In that sense, the design, synthesis, and physicochemical characterization by NMR, FTIR, DLS and TEM of two nanocarriers based on chitosan conjugates (1, non-redox-sensitive; 2, redox-sensitive) have been performed to (i) achieve the selective transport of hLDHA inhibitors into hepatocytes and (ii) their disruption once they reach the hepatocytes cytosol. Polymer 2 self-assembled into micelles in water and showed high drug loadings (19.8–24.5 %) and encapsulation efficiencies (31.9–40.8%) for the hLDHA inhibitors (I-III) tested. The non-redox-sensitive micelle 1 remained stable under different glutathione (GSH) concentrations (10 μM and 10 mM), and just a residual release of the inhibitor encapsulated was observed (less than 10 %). On the other hand, micelle 2 was sufficiently stable under in vitro physiological conditions (10 μM, GSH) but it quickly disassembled under the simulated reducing conditions present inside hepatocytes (10 mM GSH), achieving a 60 % release of the hLDHA inhibitor encapsulated after 24 h, confirming the responsiveness of the developed carrier to the high levels of intracellular GSH.LAQV@REQUIMTEDQ - Departamento de QuímicaRUNSalido, S.Alejo-Armijo, A.Parola, A. J.Sebastián, V.Alejo, T.Irusta, S.Arruebo, M.Altarejos, J.2022-12-22T22:18:43Z2022-11-052022-11-05T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article12application/pdfhttp://hdl.handle.net/10362/146554eng0378-5173PURE: 48433925https://doi.org/10.1016/j.ijpharm.2022.122224info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:27:40Zoai:run.unl.pt:10362/146554Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:52:40.509555Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Chitosan derivatives as nanocarriers for hLDHA inhibitors delivery to hepatic cells A selective strategy for targeting primary hyperoxaluria diseases |
title |
Chitosan derivatives as nanocarriers for hLDHA inhibitors delivery to hepatic cells |
spellingShingle |
Chitosan derivatives as nanocarriers for hLDHA inhibitors delivery to hepatic cells Salido, S. Chitosan Hepatocytes drug delivery hLDHA inhibitors Polymeric micelles Primary hyperoxaluria Redox-sensitive Pharmaceutical Science SDG 3 - Good Health and Well-being |
title_short |
Chitosan derivatives as nanocarriers for hLDHA inhibitors delivery to hepatic cells |
title_full |
Chitosan derivatives as nanocarriers for hLDHA inhibitors delivery to hepatic cells |
title_fullStr |
Chitosan derivatives as nanocarriers for hLDHA inhibitors delivery to hepatic cells |
title_full_unstemmed |
Chitosan derivatives as nanocarriers for hLDHA inhibitors delivery to hepatic cells |
title_sort |
Chitosan derivatives as nanocarriers for hLDHA inhibitors delivery to hepatic cells |
author |
Salido, S. |
author_facet |
Salido, S. Alejo-Armijo, A. Parola, A. J. Sebastián, V. Alejo, T. Irusta, S. Arruebo, M. Altarejos, J. |
author_role |
author |
author2 |
Alejo-Armijo, A. Parola, A. J. Sebastián, V. Alejo, T. Irusta, S. Arruebo, M. Altarejos, J. |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
LAQV@REQUIMTE DQ - Departamento de Química RUN |
dc.contributor.author.fl_str_mv |
Salido, S. Alejo-Armijo, A. Parola, A. J. Sebastián, V. Alejo, T. Irusta, S. Arruebo, M. Altarejos, J. |
dc.subject.por.fl_str_mv |
Chitosan Hepatocytes drug delivery hLDHA inhibitors Polymeric micelles Primary hyperoxaluria Redox-sensitive Pharmaceutical Science SDG 3 - Good Health and Well-being |
topic |
Chitosan Hepatocytes drug delivery hLDHA inhibitors Polymeric micelles Primary hyperoxaluria Redox-sensitive Pharmaceutical Science SDG 3 - Good Health and Well-being |
description |
Authors wish to thank the Centro de Instrumentación Científico-Técnica (CICT) of the University of Jaén, Spain, for partial financial support. A.A.-A. is grateful for the postdoctoral fellowship from Fundación Alfonso Martín Escudero. Authors acknowledge the use of the National Facility ELECMI ICTS, node “Laboratorio de Microscopias Avanzadas” at Universidad de Zaragoza. This research has also partially been supported by the Spanish Ministerio de Ciencia, Innovación y Universidades (grant RTI2018-098560-B-C22) and by the Andalusian Consejería de Economía y Conocimiento (FEDER program 2014-2020: grant number 1380682). Publisher Copyright: © 2022 The Author(s) |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-12-22T22:18:43Z 2022-11-05 2022-11-05T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/146554 |
url |
http://hdl.handle.net/10362/146554 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0378-5173 PURE: 48433925 https://doi.org/10.1016/j.ijpharm.2022.122224 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
12 application/pdf |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799138117617188864 |