Long-circulating liposomes are applied as drug carriers to minimize serious side effects of encapsulated toxic drugs. Especially polymer-coated bilayer vesicles containing a poly(ethylene glycol) (PEG) corona, known as stealth liposomes are used in clinical applications because of numerous advantages. Due to the lack of functional groups in the PEG backbone and its non-biodegradability, the development of multifunctional, biodegradable polyether-based lipids is of high interest. These structures provide possibilities for further functionalization with markers, e.g., for active targeting and carrier trafficking. We developed various cholesterol- and dialkyl-based lipids with different architectures of the hydrophilic polyether segments including linear and hyperbranched polyglycerols (hbPG) as well as copolymers with PEG for the application in liposomal formulations. Thereby, anionic ring-opening polymerization (AROP) enables the synthesis of well-defined polyether-based lipids with molecular weights in a range of 2500 to 8000 g/mol. These hetero-functional lipids were incorporated into liposomal nanocarriers which were characterized by electron microscopy imaging and dynamic light scattering. In the course of our studies the stability of the lipid anchorage, which has major implications on the overall properties of liposomes as well as the in vivo performance of the liposomes have been examined. In addition, multifunctionality of the hbPG-derived lipids permitted the attachment of fluorescent labels and target functions via orthogonal click functionalization. Recently, we reported the synthesis of biodegradable hbPG-lipids containing acid-labile acetal linkages to allow for a pH-induced cleavage of the lipids in the tissue. In conclusion, these polyether-based lipids constitute a versatile platform for the modification of liposomes and provide promising perspective to improve the performance of liposome-based drug delivery systems.

Multifunctional polyether-based lipids for liposomal nano drug carrier systems

253rd National Meeting (2017)

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