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| Verfasst von: | Witzigmann, Dominik [VerfasserIn]  |
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| | Uhl, Philipp [VerfasserIn] |
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| | Kaufman, Christina [VerfasserIn] |
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| | Schöneweis, Katrin [VerfasserIn] |
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| | Ni, Yi [VerfasserIn] |
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| | Mier, Walter [VerfasserIn] |
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| | Urban, Stephan [VerfasserIn] |
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| Titel: | Optimization-by-design of hepatotropic lipid nanoparticles targeting the sodium-taurocholate cotransporting polypeptide |
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| Verf.angabe: | Dominik Witzigmann, Philipp Uhl, Sandro Sieber, Christina Kaufman, Tomaz Einfalt, Katrin Schöneweis, Philip Grossen, Jonas Buck, Yi Ni, Susanne H. Schenk, Janine Hussner, Henriette E. Meyer zu Schwabedissen, Gabriela Québatte, Walter Mier, Stephan Urban, Jörg Huwyler |
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| E-Jahr: | 2019 |
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| Jahr: | 23 July 2019 |
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| Umfang: | 28 S. |
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| Fussnoten: | Gesehen am 06.11.2019 |
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| Titel Quelle: | Enthalten in: eLife |
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| Ort Quelle: | Cambridge : eLife Sciences Publications, 2012 |
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| Jahr Quelle: | 2019 |
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| Band/Heft Quelle: | 8(2019) Artikel-Nummer e42276, 28 Seiten |
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| ISSN Quelle: | 2050-084X |
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| Abstract: | Active targeting and specific drug delivery to parenchymal liver cells is a promising strategy to treat various liver disorders. Here, we modified synthetic lipid-based nanoparticles with targeting peptides derived from the hepatitis B virus large envelope protein (HBVpreS) to specifically target the sodium-taurocholate cotransporting polypeptide (NTCP; SLC10A1) on the sinusoidal membrane of hepatocytes. Physicochemical properties of targeted nanoparticles were optimized and NTCP-specific, ligand-dependent binding and internalization was confirmed in vitro. The pharmacokinetics and targeting capacity of selected lead formulations was investigated in vivo using the emerging zebrafish screening model. Liposomal nanoparticles modified with 0.25 mol% of a short myristoylated HBV derived peptide, that is Myr-HBVpreS2-31, showed an optimal balance between systemic circulation, avoidance of blood clearance, and targeting capacity. Pronounced liver enrichment, active NTCP-mediated targeting of hepatocytes and efficient cellular internalization were confirmed in mice by 111In gamma scintigraphy and fluorescence microscopy demonstrating the potential use of our hepatotropic, ligand-modified nanoparticles. |
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| DOI: | doi:10.7554/eLife.42276 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.7554/eLife.42276 |
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| | Verlag: https://elifesciences.org/articles/42276 |
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| | DOI: https://doi.org/10.7554/eLife.42276 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | hepatitis B virus |
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| | hepatocyte targeting |
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| | liposomes |
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| | Myrcludex B |
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| | nanocarriers |
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| | NTCP |
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| K10plus-PPN: | 1681161028 |
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| Verknüpfungen: | → Zeitschrift |
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Optimization-by-design of hepatotropic lipid nanoparticles targeting the sodium-taurocholate cotransporting polypeptide / Witzigmann, Dominik [VerfasserIn]; 23 July 2019 (Online-Ressource)
