| Background: due to the low solubility and short half-life of many existing drugs,the pharmacokinetics of low bioavailability are deficient Entrapment,in the presence of the blood-brain barrier(BBB),makes it difficult for the drug to reach the damaged brain tissue after ischemic stroke,affecting its efficacy.The drugs that do pass are also in low concentrations in brain tissue.The newly development of nanotechnology can help drug significantly expanding its pharmacokinetic limitations,in the treatment of cerebrovascular diseases has potential application value,small particle size of nanometer material,specific surface area is big,and can carries on the various target,change the character of fat-soluble,suitable for used as brain drug delivery system,also can become imaging probe.Metal organic framework(MOF)has great potential in biomedical field due to its porous structure,which is composed of metal groups and organic ligands,controllable structure,high loading efficiency and no long-term toxicity.As an essential element of life,iron has no biological toxicity,and the organic framework based on iron can carry other groups and drugs.Iron metal organic framework has been studied in the field of tumor.In this paper,the effect of iron metal organic framework with rapamycin on ischemic stroke in mice was observed.Objective: to demonstrate that the nano-iron metal organic frame can pass the blood-brain barrier and be used as drug carrier to treat MCAO model mice with rapamycin.Methods: Part I: nano-MIL-101-NH2 was synthesized by adding N,Ndimethylformamide(DMF)in hexahydrate solution of ferric chloride and 2-aminoterephthalic acid drop by drop.Mil-101-peg400 and mil-101-peg5000 were formed by PEG400 and PEG5000.Indolicyanide green was coated with mil-101-peg and used as fluorescent marker.C57 male normal mice were divided into three groups,and were injected with tail vein mil-101-peg400,mil-101-peg5000 and normal saline respectively.Furthermore,the tail vein injection of mil-101-peg5000 group was divided into three groups: MCAO group,sham group and blank group.The fluorescence levels in the brain and the main organs of living mice were observed by using near infrared apparatus.Part 2: the male C57 mice were divided into 5 groups(1.MCAO+RMOF;2.2.MCAO + MOF;3.MCAO + R;4.MCAO + DD.5.In the sham operation group+DD),the tail vein was injected with the same amount of mil-101-peg-rapamycin(RMOF).MIL-101-PEG;Rapamycin(R);Pairs of steaming water.Detectionindicators: 1.Behavior;2.2.TTC;3.Westren blot: il-1 blot and NLRP3 adaptor protein ASC in the surrounding infarct tissues.Immunofluorescence: ASC.Results: part 1: comparison of brain fluorescence in normal mice: the brain fluorescence in the tail vein of the mil-101-peg5000 group and the mil-101-peg400 group was higher than that in the blank group(p < 0.05),and that in the mil-101-peg5000 group was higher than that in the mil-101-peg400 group(p < 0.05).After injection of mil-101-peg5000 by tail vein,the brain fluorescence in MCAO model group was higher than that in sham group and normal blank mice group(p < 0.05).Part2: the carrying rate of mil-101-peg with rapamycin is 29.51±0.34%;Compared with the MCAO+RMOF group,the improvement of behavioral score and TTC staining area was not significant.However,the inflammatory index of MCAO+RMOF group was lower than that of MCAO+R group(p < 0.05),and the behavioral score,TTC staining area and inflammatory index were significantly improved in the MCAO+RMOF and MCAO+R groups compared with the MCAO+MOF and MCAO+ solvent groups(p < 0.05).Conclusion: 1.1)injection of mil-101-peg by tail vein can reach the brain tissue through the blood-brain barrier of mice.2)the effect of peg5000 through BBB is better than that of mil-101-peg after peg400.3)injection of mil-101-peg by tail vein was more efficient through BBB in ischemic stroke model.2.1).The loading rate of mil-101-peg-rapamycin on rapamycin is 30%,which is better than traditional nanomaterials.2).Mil-101-peg-rapamycin has therapeutic effect on MCAO mice,and its main therapeutic effect is derived from rapamycin;Mil-101-peg-rapamycin inhibited the inflammatory response after ischemic stroke in mice better than rapamycin alone. |
PDF Full Text Request