Optimization-by-design of hepatotropic lipid nanoparticles targeting the sodium-taurocholate cotransporting polypeptide
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 4510222
Author(s) Witzigmann, Dominik; Uhl, Philipp; Sieber, Sandro; Kaufman, Christina; Einfalt, Tomaz; Schöneweis, Katrin; Grossen, Philip; Buck, Jonas; Ni, Yi; Schenk, Susanne H.; Hussner, Janine; Meyer Zu Schwabedissen, Henriette E.; Québatte, Gabriela; Mier, Walter; Urban, Stephan; Huwyler, Jörg
Author(s) at UniBasel Huwyler, Jörg
Witzigmann, Dominik
Sieber, Sandro
Einfalt, Tomaz
Grossen, Philip
Buck, Jonas
Schenk, Susanne
Québatte, Gabriela
Hussner, Janine
Meyer zu Schwabedissen, Henriette
Year 2019
Title Optimization-by-design of hepatotropic lipid nanoparticles targeting the sodium-taurocholate cotransporting polypeptide
Journal eLife
Volume 8
Pages / Article-Number e42276
Keywords biochemistry; chemical biology; infectious disease; microbiology; mouse; rat; zebrafish
Mesh terms Animals; Drug Carriers, administration & dosage; Drug Delivery Systems, methods; Hepatitis B Surface Antigens, administration & dosage; Liposomes, administration & dosage; Liver, diagnostic imaging; Organic Anion Transporters, Sodium-Dependent, pharmacokinetics; Radionuclide Imaging; Symporters, pharmacokinetics; Zebrafish
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.
Publisher eLife Sciences Publications
ISSN/ISBN 2050-084X
edoc-URL https://edoc.unibas.ch/71773/
Full Text on edoc No
Digital Object Identifier DOI 10.7554/eLife.42276
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/31333191
ISI-Number WOS:000478937700001
Document type (ISI) Journal Article
 
   

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