Polysarcosine-based surfactants: syntheses and properties

As surfactants, amphiphilic molecules form micelles in aqueous solution to load hydrophobic medicines to increase their solubility and absorbability. TPGS, i.e. VE-PEG conjugate, is a commonly used effective surfactant suffering immune effects in human bodies with reduced biocompatibility and stealth property. Among the potential alternatives of PEG, polysarcosine (pSar) is the most promising one due to its outstanding property and effectiveness. Herein, we propose two strategies to polymerize Sar-NPC, <i>direct initialization</i> and <i>post-polymerization chain end modification</i> to conjugate hydrophobic building blocks onto pSar. <i>Direct initial­ization</i> applies amino-group-containing lipids 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) as initiators to produce DSPE-pSar and DOPE-pSar, respectively. <i>Post-polymerization chain end modification</i> changes chain end amino group of pSar to carboxyl group for esterification with the hydroxyl groups on vitamin E (VE) and 1,2-dimyristoyl-sn-glycerol (DMG) to produce VE-pSar and DMG-pSar. The degrees of polymerization of pSar blocks are designed to be 14, 25 and 28 precisely, and the CMC values of the amphiphilic products are between 0.28 and 5.63 µg/mL. VE-pSar samples have extremely strong ability to increase the solubility of paclitaxel (PTX), 30 times more than TPGS. It also exhibits high cytocompatibility and low hemolysis rate below 5%, much less than TPGS. The two preparations of pSar-containing surfactants are efficient and versatile, and the products have high probability to become a new generation of clinical hydrophobic medicine solubilizer.