Preparation And Evaluation Of Mesoporous Silica With Inflammatory Tissue Response And Effects Of Anti-inflammatory And Bone Repair

Objective:(1)Build a pH sensitive drug release of tripterygium wilfordii armor-glucosamine mesoporous silica nanoparticle drug delivery system Through the preparation of mesoporous silica,poly(dopamine coated,glucosamine graft modification such as the preparation of pH sensitive drug release double for mesoporous silica nanoparticle system,build the inflammation tissue sensitive drug release of slow-release nano preparation,to reduce drug toxicity,increase curative effect,preparation of high performance.(2)Solve the treatment of rheumatoid arthritis can’t juggle anti-inflammatory immune resistance and bone damage problem Build both anti-inflammatory and bone repair,inflammation tissue specific release of slow-release nano preparation,coordination with bone repair play antiinflammatory treatment of rheumatoid arthritis(RA),clinical treatment of rheumatoid arthritis can’t solve both anti-inflammatory and bone repair,for clinical treatment of rheumatoid arthritis,provide a new way of thinking.Method:(1)The preparation and characterization of MSN-TP@PDA-GlcN With template agent preparation of mesoporous silica nanoparticles(MSN),impregnation centrifugation load tripterygium wilfordii element(TP),and the coated poly(dopamine(PDA),finally will glucosamine(GlcN),grafting on PDA,the preparation of drug-loading nanoparticles MSN-TP @ PDA-GlcN.Using transmission electron microscopy(tem),X-ray diffraction,N2 adsorption stripping,differential thermal methods of thermogravimetric analysis of MSNs-TP@PDA-GlcN characterization analysis.Hemolysis method toinvestigate the biological safety of carrier materials.(2)The inflammatory tissue responsiveness to release The acidic environment nanoparticles drug release in vitro simulation inflammation tissues nanoparticles drug release evaluation of the inflammatory response,different pH of PBS nanoparticles in the drug release behavior of the solution,a preliminary evaluation of the organization of inflammation response;Micro dialysis method determination of drug release behavior in arthritis model in rats,investigate nanoparticles drug release of inflammatory tissue.(3)In vitro cytotoxicity and antiinflammatory effects By testing different concentrations MSN,MSNs @ PDA influence on cartilage cell vitality,examining the cytotoxicity carrier material.Testing different nanoparticles on chondrocytes under the environment of the inflammation induced by lipopolysaccharide activity,the influence of the evaluation of nanoparticles in vitro anti-inflammatory ability;ELISA kit method determination of nanoparticles on cartilage inflammation factor TNF-α,IL-1β,IL-6.(3)In vivo pharmacodynamics and safety studies Rheumatoid arthritis Wistar rat model was established,and given different drug treatment,treatment of rats toes toes swelling meter measure in volume change,and the thermal imager testing rats foot claw temperature change;Treatment ends,orbital blood,ELISA kit to determine level of inflammatory cytokines and bone related;Dislocated executed in rats,ankle joint safranin O-fast green,and joint synovial tissue for HE staining and immunohistochemical detection;Take the rat heart,liver,spleen,Lung,kidney test HE staining.Result:(1)The successful preparation of MSN-TP@PDA-GlcN nanoparticles TP in MSN-TP@PDA-GlcN drug-polymer interactions(6.78±0.81)%,GlcN drugpolymer interactions for(11.68±0.98)%,TEM,FT-IR,nitrogen stripping,thermogravimetric analysis showed that the preparation of MSN and successfully with PDA coating success.(2)The MSN-TP@PDA-GlcN inflammation of the nanoparticle has good organization responsiveness Drug release in vitro experiment,in the pH=5.0 and under the condition of pH=6.5,TP release a quantity to a significantly higher pH=7.4.Micro dialysis method collected in joint fluid retention time of drugs to nanoparticles group(36h)was obviously higher than that of free drug group(10h).(3)The MSN-TP@PDA-GlcN has good anti-inflammatory effects in vitro Nanoparticles enhance the vitality of inflammation of the synovial cells in acid,inhibit secretion of inflammatory factors TNF-α,IL-1β,IL-6.(4)The MSN-TP @PDA-GlcN in vivo pharmacodynamics and safety evaluation MSN-TP@PDAGlcN than TP+GlcN group more joint swelling(**p<0.01),relieve rheumatoid arthritis rats blood sample testing and synovial immunohistochemical display MSNTP@PDA-GlcN group of inflammatory factor lower than other treatment group(**p<0.01).X ray and safranin O-fast green results show MSN-TP@PDA-GlcN group can be a very good protection of arthritis rats relative integrity of joints.The HE staining results of all viscera exhibited no difference between the treatment group and normal group.Conclusion:(1)Preparation of MSN-TP@PDA-GlcN has good drug release properties of pH response.(2)The MSN-TP@PDA-GlcN as anti-inflammatory,bone repair effect and good biological safety for the treatment of rheumatoid arthritis provides a new dosage form selection.