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https://hdl.handle.net/1822/77032
Título: | Covalent conjugation of amphotericin B to hyaluronic acid: an injectable water-soluble conjugate with reduced toxicity and anti-leishmanial potential |
Autor(es): | Carvalho, Ricardo Emanuel Silva Leão, Teresa Gama, F. M. Tomás, Ana M. |
Data: | 13-Jan-2022 |
Editora: | American Chemical Society |
Revista: | Biomacromolecules |
Citação: | 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 |
Resumo(s): | 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. |
Tipo: | Artigo |
Descrição: | The Supporting Information is available free of charge at: https://pubs.acs.org/doi/10.1021/acs.biomac.1c01451 |
URI: | https://hdl.handle.net/1822/77032 |
ISBN: | 1526-4602 |
DOI: | 10.1021/acs.biomac.1c01451 |
ISSN: | 1525-7797 |
Versão da editora: | http://pubs.acs.org/journal/bomaf6 |
Arbitragem científica: | yes |
Acesso: | Acesso restrito UMinho |
Aparece nas coleções: | CEB - Publicações em Revistas/Séries Internacionais / Publications in International Journals/Series |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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document_55166_1.pdf Acesso restrito! | 846,35 kB | Adobe PDF | Ver/Abrir |