Janus Dendrimers to Assess the Anti-HCV Activity of Molecules in Cell-Assays
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-11-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/11/1062 |
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| author | María San Anselmo Alexandre Lancelot Julia E. Egido Rafael Clavería-Gimeno Álvaro Casanova José Luis Serrano Silvia Hernández-Ainsa Olga Abian Teresa Sierra |
| author_facet | María San Anselmo Alexandre Lancelot Julia E. Egido Rafael Clavería-Gimeno Álvaro Casanova José Luis Serrano Silvia Hernández-Ainsa Olga Abian Teresa Sierra |
| author_sort | María San Anselmo |
| collection | DOAJ |
| description | 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′-<i>bis</i>(hydroxymethyl)propionic acid (<i>bis</i>-MPA) and 2,2′-<i>bis</i>(glyciloxy)propionic acid (<i>bis</i>-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. |
| first_indexed | 2024-03-10T15:00:33Z |
| format | Article |
| id | doaj.art-2132957aa4b94befb72330b597c47d4f |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T15:00:33Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-2132957aa4b94befb72330b597c47d4f2023-11-20T20:08:42ZengMDPI AGPharmaceutics1999-49232020-11-011211106210.3390/pharmaceutics12111062Janus Dendrimers to Assess the Anti-HCV Activity of Molecules in Cell-AssaysMaría San Anselmo0Alexandre Lancelot1Julia E. Egido2Rafael Clavería-Gimeno3Álvaro Casanova4José Luis Serrano5Silvia Hernández-Ainsa6Olga Abian7Teresa Sierra8Instituto de Nanociencia y Materiales de Aragón (INMA), University of Zaragoza-CSIC, Pedro Cerbuna 12, 50009 Zaragoza, SpainInstituto de Nanociencia y Materiales de Aragón (INMA), University of Zaragoza-CSIC, Pedro Cerbuna 12, 50009 Zaragoza, SpainInstituto de Nanociencia y Materiales de Aragón (INMA), University of Zaragoza-CSIC, Pedro Cerbuna 12, 50009 Zaragoza, SpainInstituto Aragonés de Ciencias de la Salud (IACS), 50009 Zaragoza, SpainDepartamento de Farmacología y Fisiología, Facultad de Medicina, Universidad de Zaragoza, 50009 Zaragoza, SpainInstituto de Nanociencia y Materiales de Aragón (INMA), University of Zaragoza-CSIC, Pedro Cerbuna 12, 50009 Zaragoza, SpainInstituto de Nanociencia y Materiales de Aragón (INMA), University of Zaragoza-CSIC, Pedro Cerbuna 12, 50009 Zaragoza, SpainInstituto Aragonés de Ciencias de la Salud (IACS), 50009 Zaragoza, SpainInstituto de Nanociencia y Materiales de Aragón (INMA), University of Zaragoza-CSIC, Pedro Cerbuna 12, 50009 Zaragoza, SpainThe 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′-<i>bis</i>(hydroxymethyl)propionic acid (<i>bis</i>-MPA) and 2,2′-<i>bis</i>(glyciloxy)propionic acid (<i>bis</i>-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.https://www.mdpi.com/1999-4923/12/11/1062dendrimersmicellar aggregatesself-assemblydrug deliveryhepatitis Cantiviral drug |
| spellingShingle | María San Anselmo Alexandre Lancelot Julia E. Egido Rafael Clavería-Gimeno Álvaro Casanova José Luis Serrano Silvia Hernández-Ainsa Olga Abian Teresa Sierra Janus Dendrimers to Assess the Anti-HCV Activity of Molecules in Cell-Assays Pharmaceutics dendrimers micellar aggregates self-assembly drug delivery hepatitis C antiviral drug |
| title | Janus Dendrimers to Assess the Anti-HCV Activity of Molecules in Cell-Assays |
| title_full | Janus Dendrimers to Assess the Anti-HCV Activity of Molecules in Cell-Assays |
| title_fullStr | Janus Dendrimers to Assess the Anti-HCV Activity of Molecules in Cell-Assays |
| title_full_unstemmed | Janus Dendrimers to Assess the Anti-HCV Activity of Molecules in Cell-Assays |
| title_short | Janus Dendrimers to Assess the Anti-HCV Activity of Molecules in Cell-Assays |
| title_sort | janus dendrimers to assess the anti hcv activity of molecules in cell assays |
| topic | dendrimers micellar aggregates self-assembly drug delivery hepatitis C antiviral drug |
| url | https://www.mdpi.com/1999-4923/12/11/1062 |
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