Synthesis And Self-assembly Behavior Of PH-responsive Star Polymer

As for cancer treatment,chemotherapy remains the primary choice.However,the curative effect is often unsatisfactory due to the multi-drug resistance?MDR?.The rapid proliferation and growth of tumor cells over normal cells will cause two major problems:one is the need for a large amount of nutrients and vitamins,and the second is the lack of oxygen supply.The lack of vitamins allows us to use the folic acid receptor to target the drug to the tumor site.Nevertheless,the lack of oxygen will result in glycolysis to produce lactic acid,so that there is a pH gradient between the tumor cells inside and outside the compartments of the tumer cells.Based on the acid microenvironment of tumor cells,pH-responsive nanoparticles are considered as the most effective way to achieve MDR reversal.These nanoscale particles remain stable at physiological pH but disintegrate in acidic microenvironments due to hydrolysis of acid-labile bonds or protonation of chemical groups,resulting in release of the drug into the cytoplasm,causing the concentration of the drug in the cytoplasm to exceed that of the outer rotor Protein ability.At present,the study of pH-responsive nanoscale drug carriers has become a hot spot.In this paper,the pH-responsive and star drug loading system were prepared and characterized.The contents are as follows:?1?Based on the acidic microenvironmental of tumor cells,we designed and synthesized pH-responsive drug delivery materials to achieve the goal of delivering drugs and responsived releasing at tumor sites.First,the alkaline initiator was prepared by a series of reactions such as acylation,substitution,neutralization and so on,and then triggered BLG-NCA to form a four-arm polyamino acids PBLG.Finally,the PBLG and the end aldehyde group PEG?mPEG-CHO?were coupled to form the pH responsive star-like block copolymer with schiff base group at junction point under the weak alkali condition.Characterization of the structure and molecular weight distribution of the synthesized polymers by nuclear magnetic resonance?¹H NMR?and gel permeation chromatography?GPC?demonstrated the successful synthesis of pH-responsive drug delivery materials.The Schiff base micelles were analyzed by fluorescence?FL?spectroscopy,dynamic light scattering?DLS?and transmission electron microscopy?TEM?.It was found that they had lower critical micelle concentration(CMC=1.7×10^-3mg/mL)and smaller particle size?Diameter=220nm?,which is very useful as a carrier for the delivery of drugs.In addition,the drug loading capacity and in vitro release behavior of star-Schiff base micelles were studied.The results:LC?%?=25.38%,EE?%?=40.64%and DOX has a higher and faster release rate at pH 5.5.In summary,the synthesized polymer has a great potential as pH-responsive drug delivery material.?2?The intermediate polyamino acids synthesized in?1?was mixed with stearyl alcohol and mPEG?750?,and under the action of the catalyst p-toluenesulfonic acid?TsOH?,the transesterification reaction was carried out to form a star-graft copolymer four-arm PBLG-g-Stearyl Alcohol/mPEG₇₅₀.The polymer was characterized by nuclear magnetic resonance?¹H NMR?and gel permeation chromatography?GPC?,which showed the successful synthesis of star-graft copolymer.The results of fluorescence?FL?,dynamic light scattering?DLS?and transmission electron microscopy?TEM?showed that star polymer micelles had lower critical micelle concentration(CMC=1.3×10^-2)and smaller particle size?Diameter=215nm?.In addition,LC?%?=22.76%,EE?%?=72.93%,and the release study in vitro showed that the release ability of doxorubicin in pH=5.5 was significantly higher than that of pH=7.4.Therefore,the star copolymer micelles are very latent as a stable carrier for anticancer drugs.