Chitosan derivatives as nanocarriers for hLDHA inhibitors delivery to hepatic cells

Detalhes bibliográficos
Autor(a) principal: Salido, S.
Data de Publicação: 2022
Outros Autores: Alejo-Armijo, A., Parola, A. J., Sebastián, V., Alejo, T., Irusta, S., Arruebo, M., Altarejos, J.
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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spelling 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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