Synthesis and Characterization of Amphiphilic Polyphosphates with Hydrophilic Graft Chains and Cholesteryl Groups as Nanocarriers

摘要

Amphiphilic polyphosphate graft copolymers with varied densities of cholesteryl esters and hydrophilic graft chains were prepared,and the solution properties of the graft copolymers were evaluated.Polyphosphates were synthesized as backbones by ring-opening polymerization of 2-isopropyl-2-oxo-l,3,2-dioxaphospholane (IPP),2-(2-oxo-l,3,2-dioxaphosphoroyloxyethyl-2-bromoisobutyrate) (OPBB),and 2-choresteryl-2-oxo-l,3,2-dioxaphos-pholane (ChOP) using triisobutylaluminum as an initiator.Three types of polyphosphates (PIBr_xCh_y,x = number of OPBB units in a polymer;y = number of ChOP units in a polymer) such as PIBr_4,PIBr_6Ch_1,and PIBr_3Ch_2 were obtained.The molecular weights of these polymers were 2.4 x 10~4,2.4 x 10~4,and 2.6 x 10~4 g/mol,respectively.2-Methacryloyloxyethyl phosphorylcholine (MPC) was grafted from the OPBB sites in PIBr_xCh_y via atom transfer radical polymerization (ATRP) in EtOH.In each polymer system,the molecular weight of the graft polymer was linear with conversion.Furthermore,the polymer radical concentration remained constant during polymerization;that is,the molecular weights of the graft chains were easily controllable with polymerization time.The solution properties of amphiphilic PIBr_xCh_y-g-PMPCs were investigated by the methods of surface tension measurement,light scattering,and fluorescence probe.The transition point (cmc) of the surface tension of the PIBr_xCh_y-g-PMPCs aqueous solution decreased with an increase in the number of ChOP units in a graft polymer.Particularly,PIBr_3Ch_2-g-PMPC14.9K formed nanosized associates (R_h = 7.5 nm) with 2.2 molecules above 0.1 wt%.v79 cells were used to evaluate the cytotoxicity of the graft polymers,but no cytotoxicity was observed.The graft polymers containing cholesteryl groups effectively enhanced the solubility of paclitaxel in an aqueous solution.