The Preparation Of PEG-based Responsive Polymers And Their Performance

Intelligent polymeric materials,also known as stimulus-responsive polymers and environment-responsive polymer,are a kind of polymeric materials that can respond to the changes of the environment condition and take countermeasures.External environmental stimuli include temperature,pH,pressure,sound wave,ion,solvent,electric field and magnetic field,etc.Responding effectively to these stimuli,the properties of intelligent polymeric materials such as their shape and surface,their optical,mechanical and electrical parameters,their reaction features and recognition performance,change accordingly.As a kind of smart material,intelligent polymer materials have been widely used in intelligent drug delivery system,chemical converter,memory switching,sensor,artificial muscle,chemical memory,immobilization of active enzymes,tissue engineering and so on,especially in smart drug delivery system.The combination of synthetic smart polymers with biodegradable natural polymers can be developed to prepare various polymer drug carriers by cross-linking,grafting and block copolymerization.In this paper,the synthesis and application of intelligent polymers based on PEG are studied in three aspects.1.Click cyclization of linear PNIPAM-b-PEG-b-PNIPAM triblock copolymer at high concentration and the comparison of thermal-response behaviorsFirst,through two-step end-group modification of dihydroxyl-terminated PEG and single electron transfer radical polymerization of NIPAM,linear triblock copolymer of PNIPAM-b-PEG-b-PNIPAM with azido group at both block conjunctions was prepared.Click reaction between this PNIPAM-b-PEG-b-PNIPAM and one di-alkynyl small-molecule compound was carried out at high concentration.It was found that the only cyclization of PNIPAM-b-PEG-b-PNIPAM to form tadpole-like tail-(PNIPAM)2-c-PEG occurred,which is contrary to the conventional knowledge of cyclization reaction.Permanently,the cyclization reactions of linear polymers are carried out at highly thin concentration to suppress the probability of linear growth between chains,because the end of linear chain is more likely to occur inter-chain reaction at high concentration.Compared with conventional linear polymers,this linear triblock copolymer of PNIPAM-N3-PEG-N3-PNIPAM shifts its reactive groups from the chain end to the chain middle,forcing the block junctions to be closer with each other and hindering the linear growth of precursor.As well,those tail-(PNIPAM)2-c-PEG polymers exhibit different thermal-response behavior compared with their linear precursors,dependent on the block lengths of PEG and PNIPAM.2.Synthesis of hollow mesoporous silica nanoparticles modified by PCL and their switchable drug controlled release behaviorIn recent years,as a biocompatible material,mesoporous silica nanomaterials have been developed into drug-loading nano-reactor because of its highly ordered channels,high specific surface area and large pore volume.Their particle size can be controlled from 50?1000 nm,being easily uptaken by non-phagocytes.Through simple chemical modification,specific biological functional molecules can be introduced on the surface to achieve the specificity between mesoporous silica and target cells.In this thesis,hollow mesoporous silica microspheres(HMSMs)were synthesized through tetramethoxysiloxane hydrolysis by using PSt nanoparticles with narrow size distribution as the sacrificed template in the presence of cetyltrimethylamnonium bromide.The biodegradable polymer of PCL was introduced on the surface as the cap of the mesoporous channel of HMSMs,while their hollow inner cavity could bring out large drug loading.Due to the different conformations and decomposition degrees of PCL in various environments,PCL chain on the surface of HMSNs exhibited the ability to control the transmission output of meso-channels in the HMSNs layer.We studied the effects of solvent,pH and enzyme on the release behavior of adriamycin in THF,H2O,PBS solutions at different pH values with/without enzyme.3.Synthesis of PEG/PCL surface-modified hollow mesoporous silica nanoparticles and their drug controlled release behaviorThrough two-step end-group modification of methoxy PEG and ring-opening polymerization of CL,PEG-b-PCL with azido group at the block joint was obtained and then introduced onto the surface of HMSNs through azido-alkynyl click reaction to obtain the surface modified microspheres of HMSNs-g-(PEG-b-PCL).The anti-tumor drug of DOX was unloaded into the modified HMSNs in THF solution.The drug release behavior from HMSNs-g-(PEG-b-PCL)in THF,PBS buffer solutions at different pH values and with/without lipase was studied.