Multifunctional Liposomes

In contrast to conventional drug carrier systems, sterically stabilized liposomes with PEG-corona provide several advantages, such as strongly reduced mononuclear phagocyte system (MPS) uptake, prolonged blood circulation time, reduced aggregation of the PEGylated vesicles and improved stability of the liposomal formulations. Similar to PEG, linear and hyperbranched polyglycerol (lPG and hbPG) show excellent biocompatibility, but in addition offer possibilities for further functionalization. Novel types of lipids modified with hyperbranched polyglycerol (hbPG), linear-hyperbranched PEG-hbPG block copolymers and random PEG-lPG copolymers have been prepared via the combined oxyanionic polymerization of different epoxide monomers using lipophilic initiators such as cholesterol and 1,2-bis-alkylglyceryl ether. The novel amphiphilic structures were successfully included into liposomal formulations emerging 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) as colipid.


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[2] Biodegradable hyperbranched polyether-lipids with in-chain pH-sensitive linkages" S. S. Müller, T. Fritz, M. Gimnich, M. Worm, M. Helm, H. Frey, Polym. Chem. 2016, 7, 6257–6268. DOI: 10.1039/C6PY01308B.
[3] "Orthogonal Click Conjugation to the Liposomal Surface Reveals the Stability of the Lipid Anchorage as Crucial for Targeting" T. Fritz, M. Voigt, M. Worm, I. Negwer, S. S. Müller, K. Kettenbach, T. L. Ross, F. Roesch, K. Koynov, H. Frey, M. Helm, Chemistry 2016, 22, 11578–11582. DOI: 10.1002/chem.201602758.
[4] Fate of linear and branched polyether-lipids in vivo in comparison to their liposomal formulations by 18F-radiolabeling and positron emission tomography" A. T. Reibel, S. S. Müller, S. Pektor, N. Bausbacher, M. Miederer, H. Frey, F. Rösch, Biomacromolecules 2015, 16, 842–851. DOI: 10.1021/bm5017332.
[5] "Evaluation of multifunctional liposomes in human blood serum by light scattering" K. Mohr, S. S. Müller, L. K. Müller, K. Rusitzka, S. Gietzen, H. Frey, M. Schmidt, Langmuir 2014, 30, 14954–14962. DOI: 10.1021/la502926e.
[6] "Click modification of multifunctional liposomes bearing hyperbranched polyether chains" T. Fritz, M. Hirsch, F. C. Richter, S. S. Müller, A. M. Hofmann, K. A. K. Rusitzka, J. Markl, U. Massing, H. Frey, M. Helm, Biomacromolecules 2014, 15, 2440–2448. DOI: 10.1021/bm5003027.