Study on bone targeting of isoniazid-carrying nanoparticles in mice
Objective To prepare isoniazid nanoparticles using tetracycline calcium ion chelating ability as a carrier,and to investigate its bone targeting in mice.Methods Tc-plga-inh nanoparticles containing isonicazid were prepared by water-in-oil-in-water(W/O/W)method using tetracycline calcium as a carrier.The survival rate of MC-3T3-E1 cells treated with TC-PLGA at different concentrations(1 µg/mL,10 μg/mL,100 μg/mL)was evaluat-ed by CCK8 method.Hydroxyapatite adsorption assay was used to test in vitro targeting.Establish a BALB/C female mouse model and randomly divide the mice into an experimental group and a control group.The experimental group mice were injected with 24 mg/kg DiR fluorescent dye labeled TC-PLGA-INH suspension via tail vein,while the con-trol group mice were injected with an equal amount of physiological saline in the same way.And the bone targeting of isoniazid-carrying TC-PLGA-INH nanoparticles was observed by fluorescence imaging in vivo.Results TC-PLGA-INH nanoparticles containing isoniazid were synthesized successfully in this study.The particle size was(219.8±10.2)nm,the drug loading rate was(3.8+0.1)％,and the encapsulation rate was(80.9+3.9)％.The survival rate of MC-3T3-E1 cells cocultured with 100µg/ml TC-PLGA for 24 h was 95％,while the survival rate of cells at 10μg/ml and lower concentrations was greater than 80％,showing good biocompatibility.The adsorption results of hydroxyapa-tite show that the adsorption rate of targeted nanoparticles TC-PLGA-INH is close to 95％,and that of PLGA ordi-nary nanoparticles is lower than 5％.Both groups of mice reached the bones of both lower limbs 12 hours after intra-venous administration through the tail vein.After 12 h,the fluorescence intensity in bone of the experimental group was significantly higher than that of the control group,and the experimental group had sustained release and bone targeting.Conclusion The nanoparticles containing isoniazid prepared in this study have obvious slow release and bone targeting properties,and can effectively enrich the drug in the target tumor tissue.
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