Research On The Design And Application Of New Stimulus-responsive Polymers

In many applications,a material such as a polymer is required to react to a specific stimulus or trigger,stimuli-responsive polymers exhibit the special nature and performance.Stimuli-responsive polymers significantly change their properties such as solubility,shape,mechanical properties,phase separation and optical properties upon small variation of environmental conditions such as temperature,light,electric field,ultrasonic field,solvent,ions,pH etc.For example,the amphiphilic copolymers can self-assemble into core-shell architecture in an aqueous milieu.The hydrophobic block forms an inner core that provides an adequate space for the encapsulation of a large variety of hydrophobic drugs,while the hydrophilic corona forms the outer shell that protect the micelles' stability in aqueous.the external stimulation should induced the release of loaded drug molecules from the micelle core.Therefore,polymer micelles as drug delivery systems have widely used in medical field.In particular,convenient and high reliable stimulate methods become more important for stimuli-responsive polymers,include temperature,light and ultrasound.It can be carefully controlled through a number of parameters including frequency,power density and time for ultrasonic application.In contrast,shape memory polymers(SMPs),as a family of stimuli-responsive polymers,have attracted considerable attention.a typical SMPs can be programmed to fix one temporary shape and subsequently recover to its permanent shape upon stimulation(typically heat or vapor).Meanwhile,SMPs possess self-healing as additional functionalities have attracted widespread interests.The main topic of this thesis is to develop smart materials with different stimulation.The first part is the investigation of polymer micelle and PVA hydrogel as drug delivery carrier were triggered by light and ultrasonic,respectively,and the response property and drug release behavior were investigated.The second part is focused on the development zwitterionic polymers possessing both the shape memory and self-healing functionalities.In our first study regarding NIR-and UV-dual responsive behavior of amphiphilic copolymer micelles.It was shown that P(NVP-co-NHPM)could self-assemble into stable micelles in aqueous solution.The N-O photo-cleavage will induce the hydrophobic segment to release the hydrophobic moiety and cause the change of hydrophobic-hydrophilic balance,leading to the disruption of polymer micelles.Methods of UV(solution transmittance,absorption spectrum),fluorescence spectra,DLS,TEM and AFM were used to characterize the micellar disruption and controlled release processes.The result showed that dissociation of micelles can controlled by changing the irradiation intensity and irradiation time,include transmittance,average diameter and absorption intensity.For example,the turbidity change can be greater if increasing the light intensity from 0.15 to 0.41 mWcm-2(under the 511min irradiation),which is 83.0%to 95.0%,83.0%to 98.0%and 83.0%to 99.0%,respectively.By using Nile Red as the hydrophobic guest and incorporated into the micellar cores to investigate the release behavior of the micellar system under UV light irradiation,which realize micellar dissociation and controlled release processes.Moreover,the upconverting nanoparticles(NaLuF4:Gd/Yb/Tm)that can effectively absorb NIR light and convert it into visible and UV light were coloaded into polymer micelles to activate the micellar dissociation and the delivery of loaded cargoes via 980 nm NIR light.This novel light-responsive amphiphilic polymer micelles with hydrophobic photo-acid side groups will no doubt broaden the potential in the using for controlled drug delivery.In the second study,we proposed a facile and novel method to prepare hydrophobic drug loaded hydrogel,which can controllably release the drugs on-demand under ultrasound according to the parameter adjustment.Hydrophobic drug-loaded silicone oil mixing with PVA aqueous solution together to obtain a physical hydrogel after freezing/thawing treatment.Using Nile Red as the hydrophobic guest,this hydrogel showed a good morphological stability,silicone oil were dispersed in PVA hydrogel as micro-droplets,no phase separation was detected after 5 weeks by fluorescence microscope detection.The mechanical properties of hydrogel enhanced proportionally with increasing the silicone oil content,this means the silicone oil not only act as drug reservoirs dispersed within the hydrogel matrix,but also form strong adsorption effect of PVA chains on hydrophobic surfaces.Ultrasound is used to trigger the hydrophobic drug(ibuprofen)release from the hydrogel,include different freezing time,hydrogel water content,ultrasonic intensity,ultrasonic pulse and ultrasonic medium.The result showed the drugs were rapidly released with high ultrasonic intensity,or low network density,or long ultrasonic pulse,or less air dissolved in ultrasonic medium.Mechanism of ultrasound controlled drug release is studied,and the results indicate that the thermal effect can only mildly enhance the ultrasound-triggered hydrogel drug release,the mechanical effect is the main reason.Therefore,we have presented a facile and general method to prepare hydrophobic drug loaded composite hydrogel that can controllably deliver the drugs under ultrasound.This physical hydrogel can avoid the toxicity of chemical crosslinking reagent,this contribution can be readily extended to other hydrogel system and can potentially broaden the application scope of hydrogel drug delivery.In the third part,we synthesized a zwitterionic copolymer films by free radical polymerization,the monomer are sulfobetaine methacrylate(SBMA)and 2,3-dihydroxypropyl methacrylate(GMMA).Electrostatic interaction between polymer chain as reversible cross-linked fix temporary shape,and boron ester as chemically cross-linked remember a permanent temporary shape,this double-network structure have shape memory behaviors by an thermol stimulus,which was effect by temperature and sodium chloride content.Series results indicate high temperature induced well fixed rate and recovery rate.However,more salt reduce the shape memory ability,which relate to the "anti-polyelectrolyte effect" of salt ion.On the other hand,zwitterionic copolymer films exhibited excellent self-healing performance.and this performance was weaken by the addition of sodium chloride too,because the intrachain and interchain association was breaked.More importantly,In applications research,the zwitterionic copolymer materials exhibit good the anti protein adsorption with different salt ion.These results in our paper demonstrate that zwitterionic polymer own excellent shape memory,self-healing and protein resistance,and they are a promising candidate for an in vivo biomedical application platform.