Janus dendrimers to assess the anti-hcv activity of molecules in cell-assays

Anselmo, M.S. (Universidad de Zaragoza) ; Lancelot, A. ; Egido, J.E. ; Clavería-Gimeno, R. ; Casanova, Á. (Universidad de Zaragoza) ; Serrano, J.L. (Universidad de Zaragoza) ; Hernández-Ainsa, S. (Universidad de Zaragoza) ; Abian, O. (Universidad de Zaragoza) ; Sierra, T. (Universidad de Zaragoza)

Resumen: The use of nanocarriers has been revealed as a valid strategy to facilitate drug bioavailability, and this allows for expanding the drug libraries for the treatment of certain diseases such as viral diseases. In the case of Hepatitis C, the compounds iopanoic acid and 3, 3', 5-triiodothyroacetic acid (or tiratricol) were identified in a primary screening as bioactive allosteric inhibitors of viral NS3 protease, but they did not exhibit accurate activity inhibiting viral replication in cell-based assays. In this work, dendritic nanocarriers are proposed due to their unique properties as drug delivery systems to rescue the bioactivity of these two drugs. Specifically, four different amphiphilic Janus dendrimers synthesized by combining 2, 2'-bis(hydroxymethyl)propionic acid (bis-MPA) and 2, 2'-bis(glyciloxy)propionic acid (bis-GMPA) functionalized with either hydrophilic or lipophilic moieties at their periphery were used to entrap iopanoic acid and tiratricol. Interestingly, differences were found in the loading efficiencies depending on the dendrimer design, which also led to morphological changes of the resulting dendrimer aggregates. The most remarkable results consist of the increased water solubility of the bioactive compounds within the dendrimers and the improved antiviral activity of some of the dendrimer/drug aggregates, considerably improving antiviral activity in comparison to the free drugs. Moreover, imaging studies have been developed in order to elucidate the mechanism of cellular internalization.

Idioma: Inglés

DOI: 10.3390/pharmaceutics12111062

Año: 2020

Publicado en: Pharmaceutics 12, 11 (2020), 1062 [24 pp]
ISSN: 1999-4923

Factor impacto JCR: 6.321 (2020)

Categ. JCR: PHARMACOLOGY & PHARMACY rank: 29 / 275 = 0.105 (2020) - Q1 - T1

Factor impacto SCIMAGO: 1.054 - Pharmaceutical Science (Q1)

Financiación: info:eu-repo/grantAgreement/ES/DGA/B25-17R
Financiación: info:eu-repo/grantAgreement/ES/DGA-FSE/E47-20R
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/CIBERehd
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/CPII13-00017
Financiación: info:eu-repo/grantAgreement/ES/ISCIII-ERDF-ESF/PI15-00663-Investing in your future
Financiación: info:eu-repo/grantAgreement/ES/ISCIII-ERDF-ESF/PI18-00349-Investing in your future
Financiación: info:eu-repo/grantAgreement/ES/MCIU/BES-2016-078774
Financiación: info:eu-repo/grantAgreement/ES/MEC/FPU13-3870
Financiación: info:eu-repo/grantAgreement/ES/MICINN-FEDER/FPU12-05210
Financiación: info:eu-repo/grantAgreement/ES/MICINN-FEDER/PGC2018-093761-B-C31
Financiación: info:eu-repo/grantAgreement/ES/MICINN-FEDER/PGC2018-097583-B-I00

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Fisiología (Dpto. Farmacología y Fisiolog.)
Área (Departamento): Área Química Orgánica (Dpto. Química Orgánica)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)