Mesoscale Simulations On Anti-Fouling Polymer Drug Delivery Systems

The anti-fouling property is vital for the in vivo application of exogenous material. Aseffective anti-fouling materials, poly （ethylene glycol） and zwitterionic polymers are widelyused in vivo. In this work, mesoscale simulations are performed to study drug deliverysystems; drug carriers are all based on anti-fouling materials, such as PEG, zwitterionic PCBand zwitterionic P（M-Arg）; the anti-cancer drug docetaxel is employed in all systems. Thisthesis is expected to provide guidelines for the development and design of anti-fouling drugdelivery systems.All parameters in three systems are obtained through the solubility parameter method, inwhich molecular dynamics simulations are involved.The typical PLGA-PEG systems are firstly studied through dissipative particle dynamicssimulations. The effects of copolymer composition, system concentration and drug content onself-assembled morphologies are investigated. Simulation results show that whatever thecopolymer composition is, the copolymer will self-assemble into spherical core-shellstructures at certain concentrations. The self-assembled morphologies are transformed fromspherical to cylindrical, perforated lamellar and finally lamellar structures with the increase ofsystem concentration. With the growth of drug content, the self-assembled morphologiesundergo the transition from spheres to dumbbell-like and finally to cylinders. These resultssuggest that the optimal copolymer composition is PLGA₄₀-PEG₆₀. PLGA₄₀-PEG₆₀system isthe desired spherical structure at the concentration of0.1and the drug content of0.05.The differences of self-assembled morphologies between PLA-PEG and PLA-PCB withdifferent compositions are explored through dissipative particle dynamics. Subsequently, themorphologies of these two systems are compared under different concentrations. The pHresponsiveness of PLA-PCB system is also studied. The results show that whatever thecopolymer composition is, PLA-PEG systems will self-assemble into core-shell structures; asfor PLA-PCB systems, there will be onion-like and vesicle structures also. At the same blockratio of80:20, both PLA-PEG and PLA-PCB systems can self-assemble into core-shellstructures, the details of structures are different: because of amphiphilicity, some PEG chains would interact with PLA chains due to hydrophobicity, PEG shells are inhomogeneous in size;while the strong hydrophilicity of PCB makes PCB shells homogeneous.Finally, the PMMA-P（M-Arg） systems which contain arginine are studied throughdissipative particle dynamics simulations. The effects of copolymer composition andconcentration on self-assembled morphologies are investigated. Similar as the PLA-PCBsystem, the onion-like and vesicle structures are observed, the possible reason may be thestrong hydrophilicity of side chain in P（M-Arg）. The variations of self-assembled morphologyon the degree of protonation are also explored, which corresponds to different pH values ofenvironment. The results are expected to provide effective information for the assembly anddis-assembly behavior.