New stealth amphiphilic copolymers based on polysarcosine (PSar) rather than poly(ethylene glycol) (PEG) have gained more attention for their use as excipients in nanomedicine. In this study, several polysarcosine-b-poly(γ-benzyl glutamate) (PSar-b-PGluOBn) block copolymers were synthesized by ring opening polymerization (ROP) of the respective N-carboxyanhydrides (NCAs) and were characterized by Fourier-transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (H NMR) and size-exclusion chromatography (SEC). Copolymers had different PGluOBn block configuration (racemic L/D, pure L or pure D), degrees of polymerization of PSar between 28 and 76 and PGluOBn between 9 and 93, molar masses (M) between 5.0 and 24.6 kg.mol and dispersities (Đ) lower than 1.4. Nanoparticles of PSar-b-PGluOBn loaded with paclitaxel (PTX), a hydrophobic anti-cancer drug, were obtained by nanoprecipitation. Their hydrodynamic diameter (D) ranged from 27 to 118 nm with polydispersity indexes (PDI) between 0.01 and 0.20, as determined by dynamic light scattering (DLS). Their morphology was more spherical for copolymers with a racemic L/D PGluOBn block configuration synthesized at 5 °C. PTX loading efficiency was between 63 and 92 % and loading contents between 7 and 15 %. Using PSar-b-PGluOBn copolymers as excipients, PTX apparent water-solubility was significantly improved by a factor up to 6600 to 660 µg.mL.
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