Active Target Study On RGD Peptide Mediated Nano Metal Organic Framework IRMOF3 Loading Cantharidin

In this study,the toxicity of traditional Chinese medicine Chinese traditional classical(CTD)as a model drug,the load on the RGD modified with lung targeting IRMOF-3 nanoparticles(RIR),improve the toxicity of CTD at the same time,the characteristics of long-term,sustained release and targeting nano drug delivery system to the.And taking RIR as the carrier to load CTD toxic drug to do study on the entrapment and release,the pharmacokinetics and pharmacodynamics as well as the study on CTD-RIR characteristics of lung targeting.1 Verify the preparation technology of 1 IRMOF-3Repeated verification process for preparing IRMOF-3 predecessors to explore the laboratory,through infrared spectroscopy(IR),scanning electron microscopy(SEM),nitrogen adsorption and other means to re characterization of the prepared IRMOF-3,to verify the repeatability of IRMOF-3 process.IR and XRD results show that the carrier and the IRMOF-3 standard reference materials were consistent with high SEM showed that six months ago;support form and half a year after the carrier prepared by morphology particle size was between 50nm-200nm and SEM,were visible carrier shape is spherical,regular non adhesion,good dispersion;TEM and nitrogen adsorption experiment showed that the vector size is 2nm-5nm,suitable for loading drug particle size does not exceed the scope of the Hemolytic test is the standard method for the assessment of the compatibility of injection of blood,hemolysis test IRMOF-3,verify that the IRMOF-3 has good tissue compatibility.2 RGD IRMOF-3 connection with the preparation,characterization and preliminary probe targeting RIRIn this chapter,through biotechnology company chloride reaction of RGD peptide on the surface of nano metal organic framework with IRMOF-3,RGD coupled IRMOF-3(RIR)nanoparticles.By scanning electron microscopy(SEM),infrared spectroscopy(IR),mass spectrometry(MS),the qualitative analysis of RIR showed that the RGD peptide,has been successfully coupled in IRMOF-3.At the same time,the fluorescence of endoscopic confocal imaging technique(FIVE)for RIR targeting the initial detection,the results showed that:FITC labeled IRMOF-3 and RIR nanoparticles via the tail vein of mice after administration,can significantly into the lungs of mice,and the distribution in the alveolar cells around,some nanoparticles can enter into the lung cells,longer lifetime,has provided certain reference for the later vector carrying anticancer drugs for the treatment of lung cancer.3 Preparation and characterization of 3RIR nanoparticles loaded with CTD systemThe encapsulation efficiency of the nanoparticles,drug loading as evaluation index,the technology and the formulation was optimized by central composite design and response surface method combining.Process optimization results:drug concentration was 50%,drug loading time 96h,temperature 27.5 C,the speed of agitator mixer 999.5r/min,drug loading,encapsulation rate.And by scanning electron microscopy(SEM),X ray diffraction(XRD)were used to characterize the CTD-RIR nanoparticles.The results showed that:the drug loaded and SEM spectra and XRD spectra,the drug loading process had no effect on the carrier form,functional groups and structure,drug has been successfully loaded in the gap.4 CTD-RIR in vitro release kinetics and Research on freeze drying processThe forward and reverse two dynamic dialysis method,study on the drug release in pH 7.4 cells and pH 5 cells within the t?mor environment.The drug release in vitro and measure data are consistent with the Weibull equation,the fitting coefficients of R2 were 0.9671 and 0.9711,36 hours after the basic release,with slow release effect,two kinds of method of releasing the dissolution was more than 60%.By freezedrying technology to improve the water solubility and stability of CTD-RIR,the results showed that:2%mannitol and 2%poloxamer as lyoprotectant freeze-dried powder of CTD-RIR,the appearance is white powder and loose,complex solubility.And verified the three batch of the freeze-dried samples,good reproducibility,technology is worthy to be popularized.5 Pharmacokinetics of CTD-RIR nanoparticles in ratsIn the high,low doses of three CTD TC and CTD-RIR nanoparticles as the object of study,in the set time to take the rat orbital method of blood,the blood concentrations were determined by CTD HPLC,PK solver2.0 pharmacokinetic software fitting kinetic parameters of drug.The results showed that:between CTD-IRMOF-3 and CTD-RIR of all dose groups of t1/2,AUCO-t,AUCO-inf,MRTO-inf,AMMCO-inf,CL,the difference was not significant,but there was significant difference between the low dose group and TC,visible nanoparticles prolonged drug retention time.6 Study of pharmacodynamics and target of RIR nanoparticlesThis section in lung cancer model in nude mice were established,first through the tail vein injection of DIR labeled RIR nanoparticles on lung cancer in nude mice,results showed that:the concentration of RGD-RIR is higher in t?mor group,the fluorescence intensity of 4h and 12h,decreased 24h,have been effective drugs delivered to the t?mor site,indicating the target to the good.Secondly,through the test to determine tissue distribution in mice tail vein injection of CTD,CTD-IRMOF-3,RIR solution after each tissue and plasma CTD concentration,the results showed that:RIR nanoparticles increased significantly in t?mor cell distribution,significantly reduced the drug distribution in other tissues,reduce the liver and kidney toxicity of drugs,improve the drug therapeutic effect.