Computer Simulations On The PH-responsive Zwitterionic Polymer Systems For Drug Delivery

The self-assembly of responsive block copolymer has a promising application prospect in the field of drug delivery.With the help of computer simulation,we could better understand the micro/mesoscopic structure-property relationship of block copolymer and its influencing factors at the molecular level,which could provide reference and theoretical guidance for the optimal design and clinical application of the new drug delivery system.This thesis employed the dissipative particle dynamics(DPD)simulation method to study this complex soft matter system.Firstly,we investigated the self-assembly process of zwitterionic polycarboxybetaine(pCB)-based block copolymer in aqueous solution.The mechanism of drug release was also investigated under acidic conditions.The simulation results show that at a proper condition,the drug loading system can form a stable core-shell structure.With the increase of polymer concentration,the self-assembled morphology exhibits a transition from core-shell to columnar and finally to lamellar micelles.The pCB drug-loaded micelle reach the dynamic equilibrium faster and exhibits better stability than the traditional PEG-based drug-loaded system.Drug is distributed from the ring to the inside of micelle till it is completely evenly distributed in the micelle's nucleus with the increase of drug content.This structure-property relationship can provide meaningful guidance for rational drug design.Then,we systematically explored zwitterionic polysulfobetaine(pSB)-based drug-loaded system and compared it with the traditional PEG-based drug-loaded system.Also,we investigated the mechanism of drug release process at acidic conditions.From the simulation,either for blank micelle or drug-loaded micelle,pSB-based system exhibits better assembly performance than PEG-based system.Moreover,in response to concentration,the latter exhibits greater sensitivity.With increasing concentration from 5% to 50%,pSB-based systems maintain the core-shell structure and the drug are wrapped therein even though a certain degree of mergence is observed at high concentration,while PEG-based drug-loaded systems undergo the transition from core-shell to cylindrical and finally to lamellar micelles.Under acidic conditions,the core-shell micelles will disassembly,and release the anticancer drug quickly.The drug release process follows the mechanism of "swelling-demicellization-release".Finally,we explored the self-assembly structure of poly 2-methacryloyloxyethyl phosphorylcholine(PMPC)-based pH-responsive di-block copolymers,which contain the biomimetic structure of cell membrane.The effects of chain length,block ratio and polymer concentration on the equilibrium structure and drug-loading effect were investigated systematically.The formation processes of vesicle and micelle were also simulated.Results show that the equilibrium morphologies are determined by the synergistic effect of the chain length and the block ratio.The vesicular structure shows better drug loading effect than the micellar structure.At the acid condition,the drug-loaded system releases drug efficiently.