Computer Simulation On The PH-responsive Drug Delivery System Based On Zwitterionic Materials

Surface design of drug carriers is of great significance to maintain their stability,to resist nonspecific biomolecular adsorption so as to enhance in-vivo circulation time.The zwitterionic materials with cell membrane bionic structure can form superhydrophilic antifouling surface which helps to maintain colloidal stability via electrostatically induced hydration.Hence,“zwitterionization” has been developed as a new surface engineering strategy of nano-carriers.In this work,three zwitterionic drug delivery systems were used as case studies,and the dissipative particle dynamics(DPD)simulation method was employed to investigate the structure-performance relationships and the drug loading/release mechanism at micro/mesoscopic scales,which could provide design ideas and theoretical guidance for the development of novel drug delivery systems.Firstly,we studied the self-assembly process of generation-5 polyamidoamine-graftpoly(carboxybetaine methacrylate)(PAMAM(G5)-PCBMA)in aqueous solution and the loading/release mechanism of anti-cancer drug doxorubicin(DOX).The simulation results show that the PAMAM(G5)-PCBMA can spontaneously form core-shell unimolecular micelle under the neutral conditions.Within a certain drug concentration range,the drug loading efficiency(DLE)and drug loading content(DLC)showed some regularities with the raise of drug concentration.The zwitterionic PCBMA-based system has better monodisperse stability than the traditional PEGylated system.The DOX-loaded unimolecular micelle can realize the gradual release of DOX in the acidic tumor environment.Secondly,we investigated the structure-performance relationships and the DOX loading/release behaviors of the mixed-charged zwitterionic system poly(ε-caprolactone)-poly(allyl ethylene phosphate-2-(mercaptoethyl)trimethylammonium chloride/2,3-dimethyl maleic anhydride)(PCL-P(AEP-TMA/DMA)).The simulation results reveal that the spherical micelle with a core-shell structure can effectively encapsulate DOX and release the loaded DOX after entering the acidic tumor environment.Compared with the PEGylated system,the mixedcharged zwitterionic system can better load DOX in the inner core of the micelle.Finally,we explored the co-micellization behavior of the mixed polymers containing poly(2-methacryloxyethyl phosphorylcholine)(PMPC)and p H-sensitive poly(β-aminoester)(PAE)in neutral aqueous solutions.The simulation results show that the mixed polymers can be coassembled to form a mixed micelle with core-shell structure at a certain blending polymer concentration.Compared with the pure polymeric micelle and the PEGylated mixed micelle,the zwitterionic mixed micelle has improved drug loading capacity.Under acidic p H conditions,the PAE monomers are protonated,which causes the mixed micelles to deform and release the loaded DOX.