Block Copolymer Micelles Encapsulating Au(III) Bis(Dithiolene) Complexes as Promising Nanostructures with Antiplasmodial Activity
Block copolymer micelles (BCMs) can be used to improve the solubility of lipophilic drugs and increase their circulation half-life. Hence, BCMs assembled from MePEG-<i>b</i>-PCL were evaluated as drug delivery systems of gold(III) bis(dithiolene) complexes (herein AuS and AuSe) to be emp...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/3/1030 |
| _version_ | 1797609483093934080 |
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| author | Joana F. Santos Raquel Azevedo Miguel Prudêncio Fernanda Marques Yann Le Gal Dominique Lorcy Célia Fernandes |
| author_facet | Joana F. Santos Raquel Azevedo Miguel Prudêncio Fernanda Marques Yann Le Gal Dominique Lorcy Célia Fernandes |
| author_sort | Joana F. Santos |
| collection | DOAJ |
| description | Block copolymer micelles (BCMs) can be used to improve the solubility of lipophilic drugs and increase their circulation half-life. Hence, BCMs assembled from MePEG-<i>b</i>-PCL were evaluated as drug delivery systems of gold(III) bis(dithiolene) complexes (herein AuS and AuSe) to be employed as antiplasmodial drugs. These complexes exhibited remarkable antiplasmodial activity against liver stages of the <i>Plasmodium</i> <i>berghei</i> parasite, and low toxicity in a model of zebrafish embryos. To improve the complexes’ solubility, BCMs were loaded with AuS, AuSe, and the reference drug primaquine (PQ). PQ-BCMs (D<sub>h</sub> = 50.9 ± 2.8 nm), AuSe-BCMs (D<sub>h</sub> = 87.1 ± 9.7 nm), and AuS-BCMs (D<sub>h</sub> = 72.8 ± 3.1 nm) were obtained with a loading efficiency of 82.5%, 55.5%, and 77.4%, respectively. HPLC analysis and UV–Vis spectrophotometry showed that the compounds did not suffer degradation after encapsulation in BCMs. In vitro release studies suggest that AuS/AuSe-BCMs present a more controlled release compared with PQ-loaded BCMs. The antiplasmodial hepatic activity of the drugs was assessed in vitro and results indicate that both complexes present higher inhibitory activity than PQ, although encapsulated AuS and AuSe presented lower activity than their non-encapsulated counterparts. Nevertheless, these results suggest that the use of BCMs as delivery vehicles for lipophilic metallodrugs, particularly AuS and AuSe, could enable the controlled release of complexes and improve their biocompatibility, constituting a promising alternative to conventional antimalarial treatments. |
| first_indexed | 2024-03-11T06:01:01Z |
| format | Article |
| id | doaj.art-3a9351bda6964a289cc1d420fa4bcb4f |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T06:01:01Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-3a9351bda6964a289cc1d420fa4bcb4f2023-11-17T13:17:47ZengMDPI AGPharmaceutics1999-49232023-03-01153103010.3390/pharmaceutics15031030Block Copolymer Micelles Encapsulating Au(III) Bis(Dithiolene) Complexes as Promising Nanostructures with Antiplasmodial ActivityJoana F. Santos0Raquel Azevedo1Miguel Prudêncio2Fernanda Marques3Yann Le Gal4Dominique Lorcy5Célia Fernandes6Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10, km 139.7, 2695-066 Bobadela, PortugalInstituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, PortugalInstituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, PortugalCentro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10, km 139.7, 2695-066 Bobadela, PortugalInstitut des Sciences Chimiques de Rennes-UMR 6226, Université de Rennes, CNRS, ISCR, F-35000 Rennes, FranceInstitut des Sciences Chimiques de Rennes-UMR 6226, Université de Rennes, CNRS, ISCR, F-35000 Rennes, FranceCentro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10, km 139.7, 2695-066 Bobadela, PortugalBlock copolymer micelles (BCMs) can be used to improve the solubility of lipophilic drugs and increase their circulation half-life. Hence, BCMs assembled from MePEG-<i>b</i>-PCL were evaluated as drug delivery systems of gold(III) bis(dithiolene) complexes (herein AuS and AuSe) to be employed as antiplasmodial drugs. These complexes exhibited remarkable antiplasmodial activity against liver stages of the <i>Plasmodium</i> <i>berghei</i> parasite, and low toxicity in a model of zebrafish embryos. To improve the complexes’ solubility, BCMs were loaded with AuS, AuSe, and the reference drug primaquine (PQ). PQ-BCMs (D<sub>h</sub> = 50.9 ± 2.8 nm), AuSe-BCMs (D<sub>h</sub> = 87.1 ± 9.7 nm), and AuS-BCMs (D<sub>h</sub> = 72.8 ± 3.1 nm) were obtained with a loading efficiency of 82.5%, 55.5%, and 77.4%, respectively. HPLC analysis and UV–Vis spectrophotometry showed that the compounds did not suffer degradation after encapsulation in BCMs. In vitro release studies suggest that AuS/AuSe-BCMs present a more controlled release compared with PQ-loaded BCMs. The antiplasmodial hepatic activity of the drugs was assessed in vitro and results indicate that both complexes present higher inhibitory activity than PQ, although encapsulated AuS and AuSe presented lower activity than their non-encapsulated counterparts. Nevertheless, these results suggest that the use of BCMs as delivery vehicles for lipophilic metallodrugs, particularly AuS and AuSe, could enable the controlled release of complexes and improve their biocompatibility, constituting a promising alternative to conventional antimalarial treatments.https://www.mdpi.com/1999-4923/15/3/1030block copolymer micellesgold(III) bis(dithiolene) complexesdrug deliveryantimalarial drugsantiplasmodial activity |
| spellingShingle | Joana F. Santos Raquel Azevedo Miguel Prudêncio Fernanda Marques Yann Le Gal Dominique Lorcy Célia Fernandes Block Copolymer Micelles Encapsulating Au(III) Bis(Dithiolene) Complexes as Promising Nanostructures with Antiplasmodial Activity Pharmaceutics block copolymer micelles gold(III) bis(dithiolene) complexes drug delivery antimalarial drugs antiplasmodial activity |
| title | Block Copolymer Micelles Encapsulating Au(III) Bis(Dithiolene) Complexes as Promising Nanostructures with Antiplasmodial Activity |
| title_full | Block Copolymer Micelles Encapsulating Au(III) Bis(Dithiolene) Complexes as Promising Nanostructures with Antiplasmodial Activity |
| title_fullStr | Block Copolymer Micelles Encapsulating Au(III) Bis(Dithiolene) Complexes as Promising Nanostructures with Antiplasmodial Activity |
| title_full_unstemmed | Block Copolymer Micelles Encapsulating Au(III) Bis(Dithiolene) Complexes as Promising Nanostructures with Antiplasmodial Activity |
| title_short | Block Copolymer Micelles Encapsulating Au(III) Bis(Dithiolene) Complexes as Promising Nanostructures with Antiplasmodial Activity |
| title_sort | block copolymer micelles encapsulating au iii bis dithiolene complexes as promising nanostructures with antiplasmodial activity |
| topic | block copolymer micelles gold(III) bis(dithiolene) complexes drug delivery antimalarial drugs antiplasmodial activity |
| url | https://www.mdpi.com/1999-4923/15/3/1030 |
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