Preparation And Characterization Of Nanoparticles Based On Amphiphilic Star-branched Spla-b-pmpc Copolymers

Star copolymers composed of polylactide(PLA) and Poly(2-methacryloyloxyethyl phosphorylcholine)(PMPC) with asymmetric AB3 star-branched structure, symmetric A₂(B₃)₂ and A₃(B₃)₃ super-branched star structure were synthesized by the combination of the ring-opening polymerization, atom-transfer radical polymerization and click chemistry. For the synthesis of the copolymer, triazide terminated PLA (PLA-N₃) was firstly prepared by the ring-open polymerization of D, L-lactide by using the pentaerythritol triazide as initiator and Sn(Oct)₂ as catalyst. And the acetylene terminated PMPC was obtained through the atom-transfer radical polymerization of MPC, employing butynl 2-bromoisobutyrate as initiator, which was synthesized via the esterification of 3-Butyn-1-ol with 2-bromoisobutyryl bromide. The asymmetric AB3 star-branched copolymers was obtained after clicking the azide /alkyne, while the A₂(B₃)₂ and A₃(B₃)₃ super-branched star copolymers were acquired through the click reaction between acetylene terminated PMPC and two or three arms PLA-N₃, which were obtained from esterifying the hydroxyl group of PLA-N₃ with terephthaloyl chloride and 1, 3, 5-benzenetricarboxylic acid chloride, respectively. The structures of the copolymers obtained were analyzed by 1H NMR, and the results showed that the ratio of the arm numbers of PLA to that of PMPC for the three copolymers were 1:2.93,1:2.87 and 1:2.51,which were closed to the theoretical value 1:3.The self-assembly behavior of the three copolymers was investigated by fluorescence spectrum. The results demonstrated the amphiphilicity of the copolymers, and the critical aggregated concentrations of the copolymers ranged from 0.99×10-3mg/ml to 1.76×10^-3mg/ml. The copolymers with the super-branch star structure possessed a relative smaller CAC than that with asymmetric star structure.The copolymer nanoparticles were prepared by solvent evaporation and dialysis method, respectively. All three kinds of copolymers self-assembled in aqueous solution to form superamolecular aggregates of 30²00nm in size, depending on the structures of the copolymers. Symmetric super-branched star copolymer possessed a smaller size than asymmetric star-branched copolymers, probably due to the higher density of hydrophilic PMPC chains existed on the surface, which reduced the surface area of the insoluble block in the nonsolvent, and at the same time, hindered the interaction between the hydrophobic PLA chains. The Zeta potential of the three types of nanoparticles were -16.92, -16.40 and -4.31mV respectively. The nanoparticles made by A₃(B₃)₃ super-branched star copolymers exhibited a Zeta potential near to 0 mV, indicating that these nanoparticles could be a potential carrier for the drug delivery in vivo.