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Poly(Sarcosine) Surface Modification Imparts Stealth‐Like Properties to Liposomes

Bleher, Stefan and Buck, Jonas and Muhl, Christian and Sieber, Sandro and Barnert, Sabine and Witzigmann, Dominik and Huwyler, Jörg and Braz, Matthias and Süss, Regine. (2019) Poly(Sarcosine) Surface Modification Imparts Stealth‐Like Properties to Liposomes. Small, 15 (50). p. 1904716.

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Official URL: https://edoc.unibas.ch/72737/

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Abstract

Circulation lifetime is a crucial parameter for a successful therapy with nanoparticles. Reduction and alteration of opsonization profiles by surface modification of nanoparticles is the main strategy to achieve this objective. In clinical settings, PEGylation is the most relevant strategy to enhance blood circulation, yet it has drawbacks, including hypersensitivity reactions in some patients treated with PEGylated nanoparticles, which fuel the search for alternative strategies. In this work, lipopolysarcosine derivatives (BA‐pSar, bisalkyl polysarcosine) with precise chain lengths and low polydispersity indices are synthesized, characterized, and incorporated into the bilayer of preformed liposomes via a post insertion technique. Successful incorporation of BA‐pSar can be realized in a clinically relevant liposomal formulation. Furthermore, BA‐pSar provides excellent surface charge shielding potential for charged liposomes and renders their surface neutral. Pharmacokinetic investigations in a zebrafish model show enhanced circulation properties and reduction in macrophage recognition, matching the behavior of PEGylated liposomes. Moreover, complement activation, which is a key factor in hypersensitivity reactions caused by PEGylated liposomes, can be reduced by modifying the surface of liposomes with an acetylated BA‐pSar derivative. Hence, this study presents an alternative surface modification strategy with similar benefits as the established PEGylation of nanoparticles, but with the potential of reducing its drawbacks.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmaceutical Technology (Huwyler)
UniBasel Contributors:Huwyler, Jörg and Buck, Jonas and Sieber, Sandro and Witzigmann, Dominik
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Wiley
ISSN:1613-6810
e-ISSN:1613-6829
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:14 Sep 2020 06:22
Deposited On:14 Sep 2020 06:22

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