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Optimization-by-design of hepatotropic lipid nanoparticles targeting the sodium-taurocholate cotransporting polypeptide

Witzigmann, Dominik and Uhl, Philipp and Sieber, Sandro and Kaufman, Christina and Einfalt, Tomaz and Schöneweis, Katrin and Grossen, Philip and Buck, Jonas and Ni, Yi and Schenk, Susanne H. and Hussner, Janine and Meyer Zu Schwabedissen, Henriette E. and Québatte, Gabriela and Mier, Walter and Urban, Stephan and Huwyler, Jörg. (2019) Optimization-by-design of hepatotropic lipid nanoparticles targeting the sodium-taurocholate cotransporting polypeptide. eLife, 8. e42276.

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Official URL: https://edoc.unibas.ch/71773/

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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,; i.e.; 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; 111; In gamma scintigraphy and fluorescence microscopy demonstrating the potential use of our hepatotropic, ligand-modified nanoparticles.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmazeutische Technologie (Huwyler)
05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Biopharmazie (Meyer zu Schwabedissen)
UniBasel Contributors:Huwyler, Jörg and Witzigmann, Dominik and Sieber, Sandro and Einfalt, Tomaz and Grossen, Philip and Buck, Jonas and Schenk, Susanne and Québatte, Gabriela and Hussner, Janine and Meyer zu Schwabedissen, Henriette
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:eLife Sciences Publications
e-ISSN:2050-084X
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:24 Jun 2020 06:51
Deposited On:24 Jun 2020 06:51

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