Nanoparticles Based On Star-Branched PLA-b-PMPC Copolymers As Antitumor Drug Carriers

Being one of the important component of the cell membrane lipid structure,phosphorylcholine (PC) has been widely studied as the anti-clotting materials anddrug carrier. In this thesis, nanoparticles based on star copolymer composed ofpolylactic(PLA) and Poly(2-methacryloyloxyethyl phosphorylcholine)(PMPC) wereprepared by solvent evaporation methods. The morphology, size, zeta potential, andstability of the nanoparticles were characterized. The result showed that thenanoparticles possess spherical shape with the size50~100nm and neutral Zetapotential about-1.75mV under PBS buffer solution environment. The nanoparticleshave less cytotoxicity, and can be uptake by tumor cells through phagocytosis.The surface hydrophilicity of various nanoparticles was investigated by contactangle measurements. The hydrophilicity of the nanoparticles increased with thenumber of arms of PLA-b-PMPC copolymer. The two-arm and the three-arm polymernanoparticle exhibited maximum solids surface energy about72.6mN/m. The structureand surface hrdrophilicity influenced the adsorption of blood proteins onto thenanoparticles. With the increase of PMPC branched degree of PLA-b-PMPCcopolymer, the amount of bovine serum albumin (BSA) and fibrinogen (Fg) adsorptedon the nanoparticles decreased, and the three-arm PLA-b-PMPC nanoparticles has alowest adsorption amount of protein.Finally, the blood circulation, tissue distribution and tumor penetration of thenanoparticles were evaluated through animal experiments. The results showed that thethree-arm star PLA-b-PMPC polymer nanoparticles exhibited a longer bloodcirculation time compared with PLA-PEG block copolymer nanoparticles. The tissueslices and the whole-body optical imaging showed that the three-star PLA-b-PMPCpolymer nanoparticles could passive targeted to the tumor site, and had low levels inthe spleen after tail vein injection into the liver cancer-bearing mice.In summary, this study demonstrated that star-branched (PLA-b-PMPC3)3nanoparticles can be used as a carrier for the delivery of hydrophobic anticancer drugstargeting to tumor in vivo.