Encapsulation of Metronidazole in Biocompatible Macrocycles and Structural Characterization of Its Nano Spray-Dried Nanostructured Composite
Due to the great potential of biocompatible cucurbit[7]uril (CB7) and 4-sulfonatocalix[4]arene (SCX4) macrocycles in drug delivery, the confinement of the pharmaceutically important metronidazole as an ionizable model drug has been systematically studied in these cavitands. Absorption and fluorescen...
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| Format: | Article |
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MDPI AG
2021-12-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/23/7335 |
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| author | Mirella Mirankó Mónika Megyesi Zsombor Miskolczy Judit Tóth Tivadar Feczkó László Biczók |
| author_facet | Mirella Mirankó Mónika Megyesi Zsombor Miskolczy Judit Tóth Tivadar Feczkó László Biczók |
| author_sort | Mirella Mirankó |
| collection | DOAJ |
| description | Due to the great potential of biocompatible cucurbit[7]uril (CB7) and 4-sulfonatocalix[4]arene (SCX4) macrocycles in drug delivery, the confinement of the pharmaceutically important metronidazole as an ionizable model drug has been systematically studied in these cavitands. Absorption and fluorescence spectroscopic measurements gave 1.9 × 10<sup>5</sup> M<sup>−1</sup> and 1.0 × 10<sup>4</sup> M<sup>−1</sup> as the association constants of the protonated metronidazole inclusion in CB7 and SCX4, whereas the unprotonated guests had values more than one order of magnitude lower, respectively. The preferential binding of the protonated metronidazole resulted in 1.91 pH unit pK<sub>a</sub> diminution upon encapsulation in CB7, but the complexation with SCX4 led to a pK<sub>a</sub> decrease of only 0.82 pH unit. The produced protonated metronidazole–SCX4 complex induced nanoparticle formation with protonated chitosan by supramolecular crosslinking of the polysaccharide chains. The properties of the aqueous nanoparticle solutions and the micron-sized solid composite produced therefrom by nano spray drying were unraveled. The results of the present work may find application in the rational design of tailor-made self-assembled drug carrier systems. |
| first_indexed | 2024-03-10T04:47:17Z |
| format | Article |
| id | doaj.art-57b7c49876cd4614b9aeed442c1cf4a0 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T04:47:17Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-57b7c49876cd4614b9aeed442c1cf4a02023-11-23T02:50:56ZengMDPI AGMolecules1420-30492021-12-012623733510.3390/molecules26237335Encapsulation of Metronidazole in Biocompatible Macrocycles and Structural Characterization of Its Nano Spray-Dried Nanostructured CompositeMirella Mirankó0Mónika Megyesi1Zsombor Miskolczy2Judit Tóth3Tivadar Feczkó4László Biczók5Research Institute of Biomolecular and Chemical Engineering, Faculty of Engineering, University of Pannonia, Egyetem St. 10, 8200 Veszprém, HungaryResearch Centre for Natural Sciences, Institute of Materials and Environmental Chemistry, Eötvös Loránd Research Network (ELKH), P.O. Box 286, 1519 Budapest, HungaryResearch Centre for Natural Sciences, Institute of Materials and Environmental Chemistry, Eötvös Loránd Research Network (ELKH), P.O. Box 286, 1519 Budapest, HungaryResearch Institute of Biomolecular and Chemical Engineering, Faculty of Engineering, University of Pannonia, Egyetem St. 10, 8200 Veszprém, HungaryResearch Institute of Biomolecular and Chemical Engineering, Faculty of Engineering, University of Pannonia, Egyetem St. 10, 8200 Veszprém, HungaryResearch Centre for Natural Sciences, Institute of Materials and Environmental Chemistry, Eötvös Loránd Research Network (ELKH), P.O. Box 286, 1519 Budapest, HungaryDue to the great potential of biocompatible cucurbit[7]uril (CB7) and 4-sulfonatocalix[4]arene (SCX4) macrocycles in drug delivery, the confinement of the pharmaceutically important metronidazole as an ionizable model drug has been systematically studied in these cavitands. Absorption and fluorescence spectroscopic measurements gave 1.9 × 10<sup>5</sup> M<sup>−1</sup> and 1.0 × 10<sup>4</sup> M<sup>−1</sup> as the association constants of the protonated metronidazole inclusion in CB7 and SCX4, whereas the unprotonated guests had values more than one order of magnitude lower, respectively. The preferential binding of the protonated metronidazole resulted in 1.91 pH unit pK<sub>a</sub> diminution upon encapsulation in CB7, but the complexation with SCX4 led to a pK<sub>a</sub> decrease of only 0.82 pH unit. The produced protonated metronidazole–SCX4 complex induced nanoparticle formation with protonated chitosan by supramolecular crosslinking of the polysaccharide chains. The properties of the aqueous nanoparticle solutions and the micron-sized solid composite produced therefrom by nano spray drying were unraveled. The results of the present work may find application in the rational design of tailor-made self-assembled drug carrier systems.https://www.mdpi.com/1420-3049/26/23/7335drug deliveryself-assemblyhost–guest bindinginclusion complexspray drying4-sulfonatocalix[4]arene |
| spellingShingle | Mirella Mirankó Mónika Megyesi Zsombor Miskolczy Judit Tóth Tivadar Feczkó László Biczók Encapsulation of Metronidazole in Biocompatible Macrocycles and Structural Characterization of Its Nano Spray-Dried Nanostructured Composite Molecules drug delivery self-assembly host–guest binding inclusion complex spray drying 4-sulfonatocalix[4]arene |
| title | Encapsulation of Metronidazole in Biocompatible Macrocycles and Structural Characterization of Its Nano Spray-Dried Nanostructured Composite |
| title_full | Encapsulation of Metronidazole in Biocompatible Macrocycles and Structural Characterization of Its Nano Spray-Dried Nanostructured Composite |
| title_fullStr | Encapsulation of Metronidazole in Biocompatible Macrocycles and Structural Characterization of Its Nano Spray-Dried Nanostructured Composite |
| title_full_unstemmed | Encapsulation of Metronidazole in Biocompatible Macrocycles and Structural Characterization of Its Nano Spray-Dried Nanostructured Composite |
| title_short | Encapsulation of Metronidazole in Biocompatible Macrocycles and Structural Characterization of Its Nano Spray-Dried Nanostructured Composite |
| title_sort | encapsulation of metronidazole in biocompatible macrocycles and structural characterization of its nano spray dried nanostructured composite |
| topic | drug delivery self-assembly host–guest binding inclusion complex spray drying 4-sulfonatocalix[4]arene |
| url | https://www.mdpi.com/1420-3049/26/23/7335 |
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