Rapid access to polyfunctional lipids with complex architecture via oxyanionic ring-opening polymerization

Anna Maria Hofmann, Frederik Wurm, Holger Frey*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

41 Citations (Scopus)

Abstract

Polymer-coated liposomes, particularly poly(ethylene glycol) (PEG)-substituted liposomes, have emerged as long-circulating carrier systems for drug delivery and diagnostic purposes. A rapid synthesis of three different types of multifunctional lipids with structurally diverse hydrophilic, polyether-based architectures via one- or two-pot approaches is described. Architectural variation is achieved by the combination of different oxyanionic polymerization strategies and various glycidyl ether building units. Branched polyglycerol lipids have been prepared via cholesterol- or 1,2-bis-n-alkyl glyceryl ether-initiated, oxyanionic ring-opening polymerization (ROP) of protected glycidyl ethers and glycidol, respectively. In addition to these polyglycerol-based lipids, we describe the synthesis of multifunctional PEGs as the hydrophilic part of the lipid, which can be compared to conventional stealth lipids, but bear an adjustable number of hydroxyl functions within the PEG backbone. These lipids can be readily obtained by random copolymerization of ethylene oxide and protected glycidyl ethers, such as ethoxyethyl glycidyl ether (EEGE) and isopropylidene glyceryl glycidyl ether (IGG). Polydispersities Mw/Mn of the amphiphilic polyether structures were in the range of 1.04-1.2 for the linear structures and 1.1-1.6 for the hyperbranched lipids. Critical micelle concentrations (CMC) have been determined via the pyrene fluorescence method and were in the range of 1.4-40.7 mg/L, correlated to molecular weight and functionality of the polar polyether segment. Liposomes containing these hydroxy-functional lipids have been prepared via the membrane extrusion method and have been visualized by transmission electron microscopy (TEM) and cryo-TEM.

Original languageEnglish
Pages (from-to)4648-4657
Number of pages10
JournalMacromolecules
Volume44
Issue number12
DOIs
Publication statusPublished - 28 Jun 2011
Externally publishedYes

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