a Agricultural Bio-pharmaceutical Laboratory , Qingdao Agricultural University , Qingdao , China.
b National-Local Joint Engineering Laboratory , Agricultural Bio-pharmaceutical Technology , Qingdao , China.
Drug Deliv. 2018 Nov;25(1):909-915. doi: 10.1080/10717544.2018.1461958.
The aim of this study was to prepare cefquinome-loaded polylactic acid microspheres and to evaluate their in vitro and in vivo characteristics and pharmacodynamics for the therapy of pneumonia in a rat model. Microspheres were prepared using a 0.7 mm two-fluid nozzle spray drier in one step resulting in spherical and smooth microspheres of uniform size (9.8 ± 3.6 μm). The encapsulation efficiency and drug loading of cefquinome were 91.6 ± 2.6% and 18.7 ± 1.2%, respectively. In vitro release of cefquinome from the microspheres was sustained for 36 h. Cefquinome-loaded polylactic acid microspheres as a drug delivery system was successful for clearing experimental Klebsiella pneumonia lung infections. A decrease in inflammatory cells and an inhibition of inflammatory cytokines TNF-α, IL-1β and IL-8 after microspheres treatment was found. Changes in cytokine levels and types are secondary manifestations of drug bactericidal effects. Rats were considered to be microbiologically cured because the bacterial load was less than 100 CFU/g. These results also indicated that the spray-drying method of loading therapeutic drug into polylactic acid microspheres is a straightforward and safe method for lung-targeting therapy in animals.
本研究旨在制备头孢喹肟载体制备聚乳酸微球，并评价其在肺炎大鼠模型中的体外和体内特性及药效。采用 0.7mm 双流喷嘴喷雾干燥器一步法制备微球，得到球形光滑、粒径均匀的微球（9.8±3.6μm）。头孢喹肟的包封率和载药量分别为 91.6±2.6%和 18.7±1.2%。头孢喹肟从微球中的体外释放可持续 36 小时。头孢喹肟载体制备聚乳酸微球作为一种药物传递系统，成功清除了实验性肺炎克雷伯菌肺部感染。微球治疗后发现炎症细胞减少，TNF-α、IL-1β和 IL-8 等炎症细胞因子受到抑制。细胞因子水平和类型的变化是药物杀菌作用的继发表现。由于细菌负荷小于 100CFU/g，大鼠被认为具有微生物学疗效。这些结果还表明，喷雾干燥法将治疗药物载入聚乳酸微球是一种用于动物肺部靶向治疗的简单、安全的方法。
