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The Preparation And Targeting Property Preliminary Research On RGD Modified Nano Metal Organic Frameworks IRMOF-3

Posted on:2016-11-21Degree:MasterType:Thesis
Country:ChinaCandidate:Y H ZhangFull Text:PDF
GTID:2371330464456344Subject:Pharmacy
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Metal organic frameworks(MOFs)is a new type of multi-functional molecule materials developed in recent years.It is formed by the metal ions and organic ligands self-assemble,and has both organic polymer and inorganic compounds characteristics.With specific craft preparation,it was made into nano level and namely the metal organic framework NMOFs nanoparticles.Nano metal organic frameworks exhibit large pore and higher specific surface area.And the relative instability between metal and ligand bond make it has biology degradation.MOFs carry a variety of functional groups and can be modified after synthesis.Therefore,considerably NMOFs has certain feasibility as a drug carrier.1 Preparation and characterization of IRMOF-3 and RGD-1RMOF-3The research group had studied the preparation process of nanometer metal organic framework IRMOF-3.This paper carried out repeated verifications of the previous research results---the best process,and IRMOF-3 were again characterized by SEM,IR,XRD,nitrogen adsorption etc.The results show that,IRMOF-3 prepared has the correct structure,good stability,group modified by amino,nanometer level particle size,which meet the basic conditions as drug carrier.It lays the foundation for the modification and drug loaded of nano metal organic frameworks.In this paper,the RGD-IRMOF-3 metal frame according to the action between the amino of IRMOF-3 and the carboxyl groups of the RGD peptide,In addition,the RGD peptide closed amino,and get the Ac-RGD.It was characterized using the scanning electron microscope(SEM),infrared spectroscopy(IR),mass spectrometry(MS),Element analysis.Results show that the RGD peptide has been successfully coupled in IRMOF-3.2 the freeze-drying process study of nano metal organic frameworkIn order to improve the solubility and stability of nanometer metal organic frameworks IRMOF-3 in water,this paper examines the freeze-drying process of drug loaded nano metal organic frameworks.Taking 4%mannitol and 2%poloxamer as freeze-drying protective agent,the freeze-dried products had the small size,and the stability and dissolution was good,then determined the freeze-drying curve.3 the hemolysis study of drug loaded nano metal organic frameworksIn this paper,hemolysis in blood of medicine cantharidin,IRMOF-3 and RGD-IRMOF-3 were studied.The results showed that except the cantharidin,the nano metal organic framework IRMOF-3 and RGD-IRMOF-3 which loading cantharidin had good blood compatibility,they were safe in vivo.4 the target research of the RGD-IRMOF-3This paper regarded nude mice with lung cancer as the experimental animal to study the tissue distribution of CTD,IRMO'F-3 and RGD-IRMOF-3 in mice.Solution of CTD-IRMOF-3,CTD-RGD-IRMOF-3 and cantharidin were injected through mouse tail vein,detecting the concentration of cantharidin of blood and tissues by HPLC method,evaluating the distribution in mice of drug loaded nanoparticles by peak concentration ratio(Ce),the relative uptake rate(Re)and target index of drugs(Te).The results show that,the Te of RGD-IRMOF-3 was 12.02,but the Te of cantharidin and IRMOF-3 solution respectively was 0.87 and 1.16,which shows that the RGD-IRMOF-3 can target the lung tumor.Using endoscope laser confocal imaging system,FITC labeled IRMOF-3,RGD-IRMOF-3 carrier and blank FITC solution which vein injected to the mouse tail,were observed in mice vitro tissue base on cell size level.The results show that the fluorescence of IRMOF-3 and RGD-IRMOF-3 carrier groups was observed visibly.They can come into the lung cells and deep into the cancer cells.We can observe the target of carrier in cells more visually,which indirectly verified the results of the tissue distribution.It provides certain reference for the nano metal framework carrying antitumor drugs for the treatment of lung cancer in the future.
Keywords/Search Tags:nanometer metal organic framework IRMOF-3, RGD, preparation process, cantharidin, targeting research
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