Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/77032
Registo completo
Campo DC | Valor | Idioma |
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dc.contributor.author | Carvalho, Ricardo Emanuel Silva | por |
dc.contributor.author | Leão, Teresa | por |
dc.contributor.author | Gama, F. M. | por |
dc.contributor.author | Tomás, Ana M. | por |
dc.date.accessioned | 2022-04-19T17:37:36Z | - |
dc.date.issued | 2022-01-13 | - |
dc.identifier.citation | Silva-Carvalho, Ricardo; Leão, Teresa; Gama, F. M.; Tomás, Ana M., Covalent conjugation of amphotericin B to hyaluronic acid: an injectable water-soluble conjugate with reduced toxicity and anti-leishmanial potential. Biomacromolecules, 23(3), 1169-1182, 2022 | por |
dc.identifier.isbn | 1526-4602 | - |
dc.identifier.issn | 1525-7797 | por |
dc.identifier.uri | https://hdl.handle.net/1822/77032 | - |
dc.description | The Supporting Information is available free of charge at: https://pubs.acs.org/doi/10.1021/acs.biomac.1c01451 | por |
dc.description.abstract | Amphotericin B (AmB) is a highly hydrophobic drug with significant leishmanicidal activity whose use is limited by its poor water solubility and adverse effects. Polymer-drug conjugates are proposed as a delivery system designed to overcome those limitations while improving drug bioavailability, safety, and activity. Here, AmB was covalently linked to periodate-oxidized hyaluronic acid (HA) (oxidation degree of 30.1 ± 5.6%) via a Schiff base (HA-AmB imine). The conjugate presents high water solubility and self-assembles into particles with a mean size of 88.2 ± 17.6 nm, a negative charge (28.3 ± 0.9 mV), and a drug content of 17.8 ± 1.4%. Spectroscopic studies revealed the presence of AmB in aggregate and super-aggregated forms in the conjugate, which could explain the significant reduction of the in vitro cytotoxicity and hemolytic activity. The formulation showed not only in vitro anti-leishmanial activity against L. infantum-infected macrophages (IC50 = 0.023 M) but also against an in vivo infected mouse model, promoting a 1.32- and a 4.98-log10 suppression of the L. infantum burden in the spleens and liver, respectively, without toxic effects. In summary, this study describes the safe and effective use of water-soluble HA-AmB imine conjugates for leishmaniasis treatment. | por |
dc.description.sponsorship | The authors would like to acknowledge Irina Amorim from the Department of Molecular Pathology and Molecular Immunology department of ICBAS, Instituto de Ciências Biomédicas Abel Salazar, for the histopathological analysis. This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding UIDB/04469/2020 and UIDB/04293/2020 and BioTecNorte operation (NORTE-01-0145-FEDER-000004, Underpinning Biotechnology to Foster the North of Portugal Bioeconomy, and NORTE-01-0145-FEDER-000012, Structured Program on Bioengineered Therapies for Infectious Diseases and Tissue Regeneration) funded by the European Regional Development Fund (ERDF) under the scope of Norte2020. FCT and national funds (PIDDAC) through I.P/MCTES also supported this work by funding PTDC/BIA-MIC/5343/2020. The authors acknowledge the support of the i3S Scientific Platform BioSciences Screening, member of the PPBI (PPBI-POCI-01-0145-FEDER-022122) and PT-OPENSCREEN. R.S.-C. and T.L. gratefully acknowledge FCT for the granted scholarships (SFRH/BD/118880/2016 and 2020.05346.BD, respectively). | por |
dc.language.iso | eng | por |
dc.publisher | American Chemical Society | por |
dc.relation | UIDB/04469/2020 | por |
dc.relation | UIDB/04293/2020 | por |
dc.relation | PTDC/BIA-MIC/5343/2020 | por |
dc.relation | SFRH/BD/118880/2016 | por |
dc.rights | restrictedAccess | por |
dc.title | Covalent conjugation of amphotericin B to hyaluronic acid: an injectable water-soluble conjugate with reduced toxicity and anti-leishmanial potential | por |
dc.type | article | - |
dc.peerreviewed | yes | por |
dc.relation.publisherversion | http://pubs.acs.org/journal/bomaf6 | por |
dc.comments | CEB55166 | por |
oaire.citationStartPage | 1169 | por |
oaire.citationEndPage | 1182 | por |
oaire.citationIssue | 3 | por |
oaire.citationVolume | 23 | por |
dc.date.updated | 2022-03-19T10:47:43Z | - |
dc.identifier.doi | 10.1021/acs.biomac.1c01451 | por |
dc.date.embargo | 10000-01-01 | - |
dc.identifier.pmid | 35025509 | por |
dc.description.publicationversion | info:eu-repo/semantics/publishedVersion | - |
dc.subject.wos | Science & Technology | por |
sdum.journal | Biomacromolecules | por |
Aparece nas coleções: | CEB - Publicações em Revistas/Séries Internacionais / Publications in International Journals/Series |
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document_55166_1.pdf Acesso restrito! | 846,35 kB | Adobe PDF | Ver/Abrir |