The Self-assembly,Gelation And Controlled Drug Release Properties Of Temperature/pH Sensitive ABC Terpolymer

Intelligent hydrogel,also known as environmentally responsive hydrogel,its structure and phase can be changed according to external environmental condition such as temperature,pH,light,electricity and mangetic field,etc.It has broad application prospects in biosensors,medical diagnosis and drug controlled release.In recent years,the design synthesis,self-assembly,gel-sol transformation mechanism and embed-release drug properties of smart injectable hydrogels have become a research hotspot in the field of biomedical materials at home and abroad.In this paper,three different temperature/pH dual-stimuli responsive polymer hydrogels were designed and synthesized by reversible addition fragmentation chain transfer radical polymerization?RAFT?with CPDB as chain transfer agent,namely positive thermo-responsive and anion pH-responsive triblock copolymer PNIPAM₁₀₄-b-PDMA₆₁₄-b-PAA₇₅?NDA?,positive thermos-responsive and cationic pH-responsive thriblock copolymer PNIPAM₁₀₆-b-PDMA₆₁₄-b-PDMAEMA₁₇₀?NDD?,negative thermos-responsive and anion pH-responsive thriblock copolymer?ADAA?,their environmental response physicochemical properties,controlled release properties in model drug delivery systems and biological toxicity were systematically studied.The main research contents and results are as follows:?1?At low concentrations,the self-assembled nanostructures and sol-gel transition characteristics of NDA under different temperature and pH conditions were investigated by DLS,turbidity method and TEM.It was found that NDA can form different nanostructures by adjusting the temperature and pH,for example:negatively charged PNIPAM-core-shell micelle,PAA-core-linking-PNIPAM-core micelles;core1-linking-core₂ micelles.The Rheometer and SEM showed that the the polymer concentration,solution temperature and pH have a significant effect on the morphology of NDA hydrogel.when the concentration higher than 7wt%,pH=5,the NDA aqueous solution rises or falls with a slight change in temperature around 37?,showing rapid reversible sol-gel transition characteristics.On this basis,methylene blue?MB?was used as a model drug to evaluate the drug release potential by injecting a copolymer hydrogel in vitro in a simulated human environment device.MTT toxicity experiments showed that the polymer hydrogel have no significant toxicity to cells.?2?In Chapter 3,NDD triblock polymer was synthesized by changing the anionic pH-responsive block PAAin NDA to the cationic pH-responsive block PDMAEMA.The structure of NDD was determined by FTIR and ¹H NMR,the turbidity method,DLS and TEM showed that when the pH lower than THE Pka?⁷.8?of PDMAEMA,NDD changed from a small particle size hydrophilic chain to a large particle size PNIPAM-core-shell structure when temperature increased;WhenpHincreasedto9,itwasconvertedto PNIPAM-core-linking-PDMAEMA-core micelles;PDMAEMA-core₂-shell micelle when the temperature decreased.Rheometer and SEM and turbidity showed that NDD exhibited two LCST characterisitics with increasing temperature,and sol-gel reversible transformation was achieved at concentrations higher than 15wt%,pH=11and 55?.In addition,the MTT method showed that the survival rate of HELF cells in NDD hydrogel was higher than 85%,indicating that the hydrogels have good biocompatibility.?3?The ADAA triblock copolymer was prepared by changing the positive temperature sensitive block PNIPAM of NDA to negative temperature sensitive block P?AM-co-AN?.The polymer structure was determined by FTIR and ¹H NMR,the microscopic self-assembly structure of block copolymer was studied by DLS and TEM.The results show that ADAA exhibit different nanostructures in water:P?AM-co-AN?-core-shell micelle at 25?and pH higher than 7;P?AM-co-AN?-core-linking-PAA-core micelles when pH decreased;PAA-core₂-shell micelle when temperature increased.In addition,rheometer and SEM showed that the concentration,pH had a significant effect on the polymer gel-sol phase transition temperature,and the gel-sol reversible transformation can be achieved at concentration higher than 9wt%,38?and pH=7.The MTT toxicity test demonstrated that ADAA hydrogel has good biocompatibility,and the survival rate of HELF cells is 82%⁹2%.