Drug Delivery Nanocarriers Based On Dendritic Zwitterionic Unimolecular Micelles

Traditional polymer self-assembled micelles as drug carriers are prone to dissociate when they are diluted by the massive body fluids below the critical micelle concentration(CMC).And the micelles are tend to aggregate and cleaned up by the reticuloendothelial system(RES)when the non-specific protein adsorption happens.In order to improve the stability of the micelles in the complex physiological environment,we prepared dendritic zwitterionic polymer unimolecular micelles,which not only have dual sensitivity to pH and temperature,but also have good stability in the complex physiological environment.In this paper,dendritic zwitterionic polymers G3.0-g-PSBAA with different PSBAA lengths were prepared with G3.0PAMAM dendrimers as the core and poly[[3-(methacryloylamino)propyl]dimethyl-(3-sulfopropyl)ammonium hydroxide inner salt](PSBAA)as the hydrophilic shell.The structures of dendritic zwitterionic polymers G3.0-g-PSBAA were characterized and the stability of the zwitterionic unimolecular micelles in different environments were tracked and investigated.The results showed that the G3.0-g-PSBAA micelles had good monodispersity and excellent non-specific protein resistance ability.With doxorubicin(DOX)as the model drug and human hepatocellular liver carcinoma cells(HepG2 cells)as the model cells,the drug release behaviours,the cytotoxicity and the anticancer effects of the drug-loaded micelles G3.0-g-PSBAA/DOX were all studied.The results showed that the G3.0-g-PSBAA micelles had excellent biocompatibility.The drug-loaded micelles G3.0-g-PSBAA/DOX could enter the cells by endocytosis and DOX could be released from the micelles.The G3.0-g-PSBAA/DOX micelles had similar anticancer effects to the free DOX·HCl.In this paper,dendritic zwitterionic block copolymers G3.0-g-PDMAEMA-b-PSBMA with different PSBMA lengths were prepared with G3.0PAMAM dendrimers as the core and poly[[3-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide](PSBMA)and poly[2-(dimethylamino)ethyl methacrylate](PDMAEMA)as the shell.The structures of the copolymers and the stimuli responsiveness of the micelles were investigated.The results showed that G3.0-g-PDMAEMA-b-PSBMA copolymers had dual sensitivity to pH and thermo.The upper critical solution temperature(UCST)of the block copolymers could be adjusted by pH of the polymer solution,polymercomposition and polymer concentration.The phase change range of the block copolymers was relatively narrow and phase transitional behaviour of the block copolymers was relatively sensitive.The block copolymers could maintain the state of unimolecular micelles in a certain temperature range.The results of this study indicate that the zwitterionic unimolecular micelles G3.0-g-PSBAA have potential application prospects as hydrophobic drug carriers.The dendritic zwitterionic block copolymers G3.0-g-PDMAEMA-b-PSBMA have good pH and thermo responsivenesses,which makes the block copolymers also have the potential of research or application in the field of gene or drug delivery.