载异烟肼纳米微粒在小鼠体内的骨靶向性研究  

Study on bone targeting of isoniazid⁃carrying nanoparticles in mice

作　　者：冯瑞强 施江远 孙军辉 黄永胜 林毅忠 FENG Rui-qiang;SHI Jiang-yuan;SUN Jun-hui;HUANG Yong-sheng;LIN Yi-zhong(Department of Orthopedics,Jiangmen People's Hospital,Jiangmen,Guangdong Province 529000,China)

机构地区：[1]江门市人民医院脊柱关节骨病科,广东江门529000

出　　处：《解剖学研究》2024年第4期343-348,共6页Anatomy Research

基　　金：广东省医学科学技术研究基金项目(2017111092553330)。

摘　　要：目的 利用四环素钙离子螯合能力作为载体制备载异烟肼纳米微粒,考察其在小鼠体内的骨靶向性。方法 利用四环素钙离子螯合能力作为载体,采用水包油包水(W/O/W)法制备载异烟肼纳米微粒TC-PLGA-INH,CCK8法评估不同浓度(1、10、100μg/mL)TC-PLGA处理后MC-3T3-E1细胞的存活率,羟基磷灰石吸附实验测试体外靶向性。建立BALB/C雌性小鼠模型,小鼠随机分为实验组和对照组,实验组小鼠通过尾静脉注射24 mg/kg DiR荧光染料标记的TC-PLGA-INH混悬液,对照组小鼠以同样方式注射等量生理盐水。活体荧光成像观察载异烟肼纳米微粒TC-PLGA-INH在小鼠体内的骨靶向性。结果 本研究成功合成了载异烟肼纳米微粒TC-PLGA-INH,其粒径为(219.8±10.2)nm,载药率为(3.8+0.1)%,包封率为(80.9+3.9)%。用100μg/ml TC-PLGA共培养24 h的MC-3T3-E1细胞的细胞生存率值为95%,而在10μg/ml及其更低浓度表明细胞生存率均大于80%,显示出很好的生物相容性。羟基磷灰石吸附实验结果表明,靶向性纳米粒TC-PLGA-INH吸附率接近95%,PLGA普通纳米粒低于5%。两组小鼠通过尾静脉静脉给药12 h后到达双下肢骨骼。12 h后,实验组在骨骼中的荧光强度明显高于对照组,且实验组具有缓释性和骨靶向性。结论 本研究所制备的载异烟肼纳米微粒具有明显的缓释性与骨靶向性,能将药物有效富聚于靶区肿瘤组织中。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(1μg/mL,10μg/mL,100μg/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 enric

关 键 词：异烟肼 纳米微粒 四环素 载体 骨靶向性 

分 类 号：R96[医药卫生—药理学]