Preparation And Application Of Poly(N-isopropyl Acrylamide)-based Microgels By High-gravity Method

Poly(N-isopropyl acrylamide)(PNIPAM)microgels with a lower critical solution temperature(LCST,～32℃)close to the physiological temperature,has broad application prospects in drug delivery,tissue engineering and biosensors.Microgel size and structure are vital parameters influencing the properties and performance of stimuli-responsive microgels.Highly precise particle size and structure customization is an essential desire for specific applications of microgels.Mixing and strong shearing in the reactor play a key role in the polydispersity and particle growth of microgels.Therefore,it is necessary to realize efficient and controllable preparation of PNIPAM-based functional microgels.In this paper,high-gravity rotating packed bed(RPB)reactor was used to enhance mass transfer and molecular mixing,and generate strong shearing.The research on controllable preparation of PNIPAM-based microgels by high-gravity technology intensified precipitation polymerization was carried out.Copolymerized smart microgels,degradable core-shell nanocomposites,interpenetrating microgels and PNIPAM-based microgel-hydrogel composites with tunable multifunctionality were prepared,and their applications in drug delivery,tissue engineering,local drug delivery and hydrogel sensors were explored.The main research content and innovations of this paper are as follows:(1)PNIPAM-based microgels were prepared by precipitation polymerization intensified by high-gravity technology.In RPB,PNIPAM microgel size could be controlled in nanoscale by adjusting the higee level(β),which is difficult to achieve in the conventional precipitation polymerization without surfactant.By varying theβfrom 20 to 324,the particle size was tailored from 129 to 325 nm and the D_h was tailored from 217.7 to 805.4 nm.The microgel size was also synergistically controlled by adjusting the amount of cross-linker and initiator.Contrast with traditional stirring polymerization,RPB synthesis procedure could obtain high yield within only 2 h of reaction time.The polydispersity index(PDI)of all PNIPAM microgels prepared by RPB was less than 0.1,exhibiting good monodispersity.Repeated experiments indicated that the RPB method showed good reproducibility.Furthermore,NIPAM was copolymerized with different functional monomers to regulate the LCST and microgel size.PNIPAM-based smart microgels showed good biocompatibility,and could realize the effective loading and sustained/controlled release of doxorubicin hydrochloride(DOX).(2)Polydopamine@poly(N-isopropylacrylamide)-tannic acid(PDA@PNIPAM-TA)nanocomposites with core-shell structure were prepared by seed precipitation polymerization intensified by high-gravity technology.The nanocomposites exhibited obvious and reversible temperature/near-infrared(NIR)light dual-stimuli responsiveness.As expected,relatively complete degradation could be achieved by changing the pH of degradation medium and extending the degradation time.Benifitting by TA and PDA rich in polyphenolic groups,the nanocpmposites significantly improved the foliar adhesion of droplets.Further using them as pesticide delivery systems,the PDA cores provided more imidacloprid(IMI)adsorption active sites and excellent photothermal effects.The PNIPAM-TA shells served as a container for IMI loading and a temperature-sensitive switch for IMI release,thereby achieving temperature/NIR light-controlled release and switching on/off release of IMI.Changing the particle size of PDA core and the thickness of PNIPAM-TA shell could regulate the loading and release behavior of IMI.(3)PNIPAM/polymethacrylic acid(PMAA)microgels with interpenetrating network(IPN)structure were prepared by low temperature free radical polymerization in an RPB reactor.Due to the intensification of high-gravity technology,the reaction time was shortened to 15-20 min.The hydrophilic PMAA polymer chains were introduced into the PNIPAM microgel three-dimensional network as the second scaffold network.The smaller the PNIPAM microgel size,the smaller the IPN microgel size and the more obvious the reduction of dehydration shrinkage.The high content of PMAA polymer chains broadened the phase transition temperature range of IPN microgels.IPN microgels with smaller PNIPAM microgel size and lower content of PMAA polymer chains possessed lower critical gelation concentration;IPN microgels with higher content of PMAA possessed lower critical gelation temperature.The preferred PNIPAM/PMAA IPN microgel dispersion had a critical gelation concentration of 2.5 wt%and a critical gelation temperature of 34℃.PNIPAM/PMAA IPN microgels exhibited excellent injectability,good biocompatibility and drug release performance.The non-flowing physical crosslinked hydrogel formed by IPN microgel dispersion undergoing the“sol-gel”transition under simulated physiological conditions could achieve more slow and long-term release of DOX.(4)A simple and effective strategy for constructing PNIPAM-based microgel-hydrogel composites with tunable multifunctionality was developed.Inspired by the construction of nanostructures in hydrogel and the adhesion mechanism of natural mussels,the activated PNIPAM microgels,silver nanowires and PDA were integrated into the poly(N-isopropyl acrylamide-acrylamide)(P(NIPAM-AM))hydrogel matrix through in-situ polymerization,and the mechanically strengthened and multifunctional conductive hydrogels were prepared.The optimal reaction conditions were:the amount of N,N’-methylenebisacrylamide(BIS)was 0.025 mol%,the content of activated PNIPAM microgels was 2.5%,the content of silver nanowires was 0.54-0.81%,and the content of PDA was 0.13-0.39%.Among them,PNIPAM-based microgel-hydrogel were used as temperature-responsive components,PDA and silver nanowires were used as NIR light-responsive components,and silver nanowires also acted as conductive components,which endowed composite hydrogels with temperature/NIR light dual-stimuli responsiveness and conductivity.In addition,the composite hydrogels exhibited excellent extensibility,tissue adhesion,self-healing ability,in vitro antioxidant capacity,biocompatibility and antibacterial activity.The composite hydrogel was simply assembled into a hydrogel sensor,which could monitor the tensile strain and finger bending movement in real time.The hydrogel sensor also exhibited sensitive strain sensing and long-lasting electrical stability during both continuous and gradual cycling processes.