Preparation Of PNIPAM-Based Nanocarrier And Application In NIR Light Controlled Drug Release

With the rapid development of nanotechnology,intelligent drug delivery systems(IDDS)based on nanocarriers have been widely concerned and researched.However,most domestic and foreign researches in the field of IDDS focus on the regulation of independent endogenous stimulus or exogenous stimulus.This single controlled drug release system is prone to form an internal closed-loop system and cannot participate in the targeted controlled release of drugs through simple external means.Therefore,it is of great practical significance to conduct more in-depth research on the potential mechanisms involved in the synergistic effect of internal and external stimuli or the cascade effect of multiple stimuli,and developing more systematic and comprehensive IDDS based on exogenous and endogenous stimuli has important application value.Based on this,the surface modification or structure design of poly(N-isopropylacrylamide)(PNIPAM)based microgels were carried out to synthesize microgel drug carrier with different characteristics,and introduced near infrared(NIR)photothermal conversion agent graphene oxide(GO)or polydopamine(PDA)in different systems to endow the system with NIR temperature cascade response ability,so as to realize the light controlled release of single or dual drugs.Firstly,microgel copolymerized by PNIPAM and acrylic acid(AA)(PNIPAM-coAA)was prepared by emulsion polymerization method,which was used as a nanocarrier loaded with 5-fluorouracil(5-FU),and the photothermal conversion agent GO was introduced into the microgels suspension system to endow the system with NIR photoresponse performance,and its drug release performance was tested.The results showed that PNIPAM-co-AA has significant temperature and p H sensitivity.When the content of AA was 5%,its volume phase transition temperature(VPTT)was 40°C,and the surface Zeta potential was-8.28 m V.The presence of GO makes the system have a sensitive NIR response performance.When the GO content was 5%,the photothermal conversion performance test showed that the PNIPAM-co-AA/GO system can reach above 40°C within 3 min,with stable and recyclable conversion efficiency.The drug release experiment showed that under the stimulation of NIR,the cumulative release rate of 5-FU in the PNIPAM-co-AA/GO system reached 77.24% after 24 h at p H 7.4,25°C,and the presence of GO delayed the drug release equilibrium time by more than 5 h.This system has a drug controlled release performance specific to the human intestinal environment.Secondly,drug loaded microgels and photothermal conversion agent GO were introduced into sodium alginate(SA)to prepare SA based composite hydrogel for NIR photo controlled drug release of in vitro dressing.Quaternary ammonium modified cationic microgel(QAS-P)was prepared by soapless emulsion polymerization.As a nanocarrier,the anionic drug diclofenac sodium(DS)was loaded by the positive charge carried by the quaternary ammonium group,giving SA hydrogel certain antibacterial ability.The analysis showed that the optimal ratio of the synthesized microgels was obtained as molar ratio 1-vinylimidazole(VIM): 1,6-dibromohexane(DH)=1: 2.At this time,VPTT of QAS-P microgel was 40°C,and the surface Zeta potential was 14.77 m V.When the GO content was 5%,the local temperature of the composite hydrogel can be increased to 41.1°C within 120 s.The results showed that SA/QAS-P/GO composite hydrogel had significant NIR responsive drug release performance by controlling the change of drug release conditions.When exposed to NIR,GO photothermal conversion caused local temperature rise of the hydrogel.When the temperature exceeded the VPTT of QAS-P drug loaded microgel,QAS-P released drug DS into the composite hydrogel through rapid volume contraction and rapid release through swelling of the composite hydrogel.NIR controlled release of drugs in hydrogel dressings was preliminarily realized.Finally,in order to improve the NIR photothermal conversion efficiency of the composite hydrogel and achieve the controlled release of two drugs,a core-shell microgel with PDA nanoparticles as the core and QAS-P microgel as the shell(PDA@QAS-P)was prepared by seed emulsion polymerization,and its NIR light controlled dual drug release performance was tested.The results showed that the diameter of the PDA core of the composite microgel was about 300 nm,the thickness of the QAS-P shell was about 100 nm,the VPTT was 40°C,and the surface Zeta potential was 15.82 m V.When PDA@QAS-P microgel content accounts for SA/PDA@QAS-P When 50% of the composite hydrogel was used,the local temperature of the composite hydrogel can be increased to 48.6°C within 120 s,and the photothermal conversion effect can be significantly improved.The antibacterial drug minocycline(MINO)was loaded into the SA matrix,drug DS was loaded in the microgels,and the dual drug release performance was carried out.The results showed that MINO was released freely with the swelling of the hydrogel,while DS was released under the control of NIR light.In the four NIR laser cycles,the cumulative release rate of DS was increased by 13.85%,8.71%,8.07% and5.42%,respectively,indicating that the existence of core-shell microgels in the hydrogel system make it have a more effective NIR light controlled release behavior,and realize the segmented controlled release of both inner and outer layers of drugs.The application of NIR temperature multi stimulation cascade control in dual drug controlled release in this topic provides certain research value for the design of photoresponsive multi drug release systems.