Preparation Of NIR Triggered Nanocarriers With Upper Critical Solution Temperature And Applications In Drug Delivery

Drug delivery system(DDS)not only solves the problems of normal tissue toxicity,poor biocompatibility,short circulation time,unsatisfactory distribution and metabolic clearance in the body,but also can help achieve controlled release of drugs during the process of drug delivery.Polymers with upper critical solution temperature(UCST)have great potential for drug delivery due to their phase transition properties showing hydrophilicity above the critical temperature(clearing point)and hydrophobicity below it.Regarding the traditional and diverse stimulusresponsive methods,near infrared(NIR)is becoming more and more popular due to its exogenous controllability,excellent tissue penetration ability,safety,non-invasiveness,convenience and easy operation.Therefore,in this thesis,two NIR responsive drug delivery systems were constructed by combining temperature-responsive polymers and photothermal agents.Their controllable drug release properties in the process of drug delivery were studied in detail.It mainly included the following two parts:First,the hollow mesoporous silica nanoparticles(HMSNs)were prepared by the template method with visible hollow cavity and mesoporous on the shell.UCST polymer P(NAGA-coNPh Am)was obtained through reversible addition-fragmentation chain transfer(RAFT)polymerization.The clearing point test and dynamic light scattering(DLS)test results showed that it had a typical UCST-type phase transition behavior,with a clearing temperature point of 45 °C.Subsequently,the polymer P(NAGA-co-NPh Am)was grafted to the surface of HMSNs by amidation reaction as a "gatekeeper" of mesoporous to achieve controlled drug release.The results of TEM,fourier transform infrared spectroscopy(FTIR)and thermogravimetric analysis(TGA)all indicated the successful preparation of polymer modified HMSNs.A NIR responsive drug delivery system was established by loading anti-cancer drug doxorubicin hydrochloride(DOX)and photothermal conversion agent indocyanine green(ICG)in the nanoparticles cavities.The drug delivery system exhibited excellent photothermal performance and ideal drug release performance under NIR stimulation.In addition,it showed good biocompatibility in the phagocytosis experiment of human breast cancer cells(MCF-7).Finally,the toxicity test result showed that the drug delivery system had low cytotoxicity,and could effectively release DOX under NIR irradiation.Moreover,photothermal therapy and chemotherapy was observed in the treatment of cancers.Then,we used a macromolecular initiator(PEG-DDMAT)to initiate RAFT polymerization and obtained polymer PEG-b-P(NAGAm-co-NPh Am)with amphiphilic molecular chains at room temperature.A NIR triggered drug delivery system was established by loading diabetes drug metformin hydrochloride(Met)and photothermal conversion agent ICG in polymer vesicles during the self-assembly process.The cloud point test result showed that it had a typical UCSTtype phase transition behavior,and the clearing point was about 41 °C.Meanwhile,TEM and DLS results showed the successful assembly of polymer vesicles.In the photothermal test and drug release test,the as-prepared drug delivery system showed excellent photothermal performance and controlled drug release performance.Subsequently,the polymer vesicle drug delivery system was integrated into a water-soluble PVA/PVP microneedle through the template method,and the results of skin penetration test and mechanical experiment showed an excellent mechanical property of microneedle.Photothermal test results of diabetic rat model administration skin area showed a good photothermal performance.Finally,in the diabetic rat model,this NIR triggered drug delivery system showed a sustained-release effect and an ability of blood glucose levels control after administration through microneedles.