Polysarcosine-Based Lipids: From Lipopolypeptoid Micelles to Stealth-Like Lipids in Langmuir Blodgett Monolayers

摘要

Amphiphiles and, in particular, PEGylated lipids or alkyl ethers represent an important class of non-ionic surfactants and have become key ingredients for long-circulating (“stealth”) liposomes. While poly-(ethylene glycol) (PEG) can be considered the gold standard for stealth-like materials, it is known to be neither a bio-based nor biodegradable material. In contrast to PEG, polysarcosine (PSar) is based on the endogenous amino acid sarcosine ( N -methylated glycine), but has also demonstrated stealth-like properties in vitro, as well as in vivo. In this respect, we report on the synthesis and characterization of polysarcosine based lipids with C 14 and C 18 hydrocarbon chains and their end group functionalization. Size exclusion chromatography (SEC) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis reveals that lipopeptoids with a degree of polymerization between 10 and 100, dispersity indices around 1.1, and the absence of detectable side products are directly accessible by nucleophilic ring opening polymerization (ROP). The values for the critical micelle concentration for these lipopolymers are between 27 and 1181 mg/L for the ones with C 18 hydrocarbon chain or even higher for the C 14 counterparts. The lipopolypeptoid based micelles have hydrodynamic diameters between 10 and 25 nm, in which the size scales with the length of the PSar block. In addition, C 18 PSar 50 can be incorporated in 1,2-distearoyl- sn -glycero-3-phosphocholine (DSPC) monolayers up to a polymer content of 3%. Cyclic compression and expansion of the monolayer showed no significant loss of polymer, indicating a stable monolayer. Therefore, lipopolypeptoids can not only be synthesized under living conditions, but my also provide a platform to substitute PEG-based lipopolymers as excipients and/or in lipid formulations.