Poly(trimethylene carbonate)/Poly(malic acid) Amphiphilic Diblock Copolymers as Biocompatible Nanoparticles

摘要

Amphiphilic polycarbonate-poly(hydroxyalkanoate) diblock copolymers, namely, poly(trimethylene carbonate) (PTMC)-b-poly(-malic acid) (PMLA), are reported for the first time. The synthetic strategy relies on commercially available catalysts and initiator. The controlled ring-opening polymerization (ROP) of trimethylene carbonate (TMC) catalyzed by the organic guanidine base 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), associated with iPrOH as an initiator, provided iPrO-PTMC-OH, which served as a macroinitiator in the controlled ROP of benzyl -malolactonate (MLABe) catalyzed by the neodymium triflate salt (Nd(OTf)(3)). The resulting hydrophobic iPrO-PTMC-b-PMLABe-OH copolymers were then hydrogenolyzed into the parent iPrO-PTMC-b-PMLA-OH copolymers. A range of well-defined copolymers, featuring different sizes of segments (M-n,M-NMR up to 9300gmol(-1); D-M=1.28-1.40), were thus isolated in gram quantities, as evidenced by NMR spectroscopy, size exclusion chromatography, thermogravimetric analysis, differential scanning calorimetry, and contact angle analyses. Subsequently, PTMC-b-PMLA copolymers with different hydrophilic weight fractions (11-75%) self-assembled in phosphate-buffered saline upon nanoprecipitation into well-defined nano-objects with D-h=61-176nm, a polydispersity index <0.25, and a negative surface charge, as characterized by dynamic light scattering and zeta-potential analyses. In addition, these nanoparticles demonstrated no significant effect on cell viability at low concentrations, and a very low cytotoxicity at high concentrations only for PTMC-b-PMLA copolymers exhibiting hydrophilic fractions over 47%, thus illustrating the potential of these copolymers as promising nanoparticles.