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为将汉防己甲素(tetrandrine,Tet)经呼吸道输送至病变部位,该文制备了一种具有“内嵌”聚乳酸羟基乙酸共聚物(PLGA)纳米粒子的复合微球,并对其形貌、释药性能、细胞毒性、细胞摄取等进行了研究。采用乳化扩散溶剂挥发法制备了载Tet的PLGA纳米粒子,以甘露醇为基质,运用喷雾干燥法制备了复合微球。采用扫描电子显微镜、动态光散射激光粒度仪、共聚焦显微镜对其性状、粒径进行表征。运用反相高效液相法对复合微球的载药量、包封率、释药特性进行了考察,采用MTT法对复合微球与Tet原料药的细胞毒性进行了对比,并用共聚焦显微镜观察了微球的细胞摄取行为。结果显示所制备的复合微球粒径为1~3μm,处在最佳沉降粒径之间,“内嵌”的PLGA纳米粒子粒径为189 nm,在模拟人肺部环境下,复合微球快速溶蚀,释放出单分散性良好的纳米粒子。与Tet原料药相比,复合微球具有一定的缓释性能,对肺癌A549细胞有更强的细胞毒性。细胞摄取实验表明细胞对纳米粒子有较强的透膜能力,摄取过程呈时间依赖性。该研究为开发新颖的肺癌化疗给药系统提供了依据。
In order to transport tetrandrine (Tet) to diseased sites through the respiratory tract, a composite microspheres with “inlaid ” polylactic acid glycolic acid copolymer (PLGA) nanoparticles was prepared and its Morphology, drug release properties, cytotoxicity, cellular uptake and so on. The Tet-loaded PLGA nanoparticles were prepared by emulsion diffusion solvent evaporation method. The composite microspheres were prepared by spray drying using mannitol as the substrate. The properties and particle size of the particles were characterized by scanning electron microscopy, dynamic light scattering laser particle size analyzer and confocal microscopy. The drug loading, entrapment efficiency and drug release characteristics of the composite microspheres were investigated by RP-HPLC. The cytotoxicity of the composite microspheres with Tet was compared by MTT method. The cytotoxicity of the composite microspheres was evaluated by confocal microscopy The microsphere’s cellular uptake behavior. The results showed that the size of the prepared composite microspheres was 1 ~ 3μm, which was between the optimum sedimentation particle size. The diameter of the PLGA nanoparticle embedded in “” was 189 nm. Under simulated human lung environment, Rapid dissolution of the microspheres, the release of a good monodisperse nanoparticles. Compared with the Tet drug substance, the composite microspheres have certain sustained-release properties and are more cytotoxic to lung cancer A549 cells. Cell uptake experiments show that the cells have a strong ability to penetrate the nanoparticles, the process of uptake is time-dependent. The research provides the basis for the development of novel lung cancer chemotherapy delivery system.