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PDMS-b-PMOXA polymersomes for hepatocyte targeting and assessment of toxicity
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 3884007
Author(s) Kiene, Klara; Schenk, Susanne H.; Porta, Fabiola; Ernst, Alexandra; Witzigmann, Dominik; Grossen, Philip; Huwyler, Jörg
Author(s) at UniBasel Huwyler, Jörg
Kiene, Klara
Schenk, Susanne
Porta, Fabiola
Witzigmann, Dominik
Grossen, Philip
Year 2017
Title PDMS-b-PMOXA polymersomes for hepatocyte targeting and assessment of toxicity
Journal European Journal of Pharmaceutics and Biopharmaceutics
Volume 119
Pages / Article-Number 322-332
Keywords PDMS-b-PMOXA, Polymersomes, Drug release, Targeted drug delivery,, Asialoglycoprotein receptor, Asialofetuin, Toxicity, Zebrafish
Abstract Nanoparticles, such as polymersomes, can be directed to the hepatic asialoglycoprotein receptor to achieve targeted drug delivery. In this study, we prepared asialofetuin conjugated polymersomes based on the amphiphilic di-block copolymer poly(dimethylsiloxane)-b-poly(2-methyloxazoline) (PDMS-b-PMOXA). They had an average diameter of 150nm and formed monodisperse vesicles. Drug encapsulation and sustained release was monitored using the hydrophilic model compound carboxyfluorescein. Asialoglycoprotein receptor specific uptake by HepG2 cells in vitro was energy dependent and could be competitively inhibited by the free targeting ligand. Mechanistic uptake studies revealed intracellular trafficking of asialofetuin conjugated polymersomes from early endosomes and to the lysosomal compartment. Polymersomes showed no toxicity in the MTT assay up to concentrations of 500μg/mL. In addition, acute toxicity and tolerability of our PDMS-b-PMOXA polymersome formulations was assessed in vivo using zebrafish embryos as a vertebrate screening model. In conclusion, a hepatocyte specific drug delivery system was designed, which is safe and biocompatible and which can be used to implement liver-specific targeting strategies.
Publisher Elsevier
ISSN/ISBN 0939-6411 ; 1873-3441
edoc-URL http://edoc.unibas.ch/55721/
Full Text on edoc No
Digital Object Identifier DOI 10.1016/j.ejpb.2017.07.002
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/28720487
ISI-Number 000412041500033
Document type (ISI) Journal Article
 
   

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17/06/2024