College of Chemistry and Pharmaceutical Sciences, Qingdao Agricultural University, Qingdao, 266109, China.
National-Local Joint Engineering Laboratory of Agricultural Bio-pharmaceutical Technology, Qingdao, 266109, China.
Pharm Res. 2019 Mar 28;36(5):74. doi: 10.1007/s11095-019-2614-7.
This study aimed to compare in vivo activity between cefquinome (CEQ)-loaded poly lactic-co-glycolic acid (PLGA) microspheres (CEQ-PLGA-MS) and CEQ injection (CEQ-INJ) against Klebsiella pneumonia in a rat lung infection model.
Forty-eight rats were divided into control group (sham operated without infection and drug treatment), Klebsiella pneumonia model group (KPD + Saline), CEQ-PLGA-MS and CEQ-INJ therapy groups (KPD + CEQ-PLGA-MS and KPD + INJ, respectively). In the KPD + Saline group, rats were infected with Klebsiella pneumonia ATCC 10031. In the KPD + CEQ-PLGA-MS and KPD + INJ groups, infected rats were intravenously injected with 12.5 mg/kg body weight CEQ-PLGA-MS and CEQ-INJ, respectively.
Compared to CEQ-INJ treatment group, CEQ-PLGA-MS treatment further decreased the number of bacteria colonies (decreased to 1.94 lg CFU/g) in lung tissues and the levels of inflammatory cytokine including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-4 (p < 0.05 or p < 0.01) in bronchoalveolar lavage fluid at 48 h. Consistently, a significant decreases of scores of inflammation severity were showed at 48 h in the KPD + CEQ-PLGA-MS treatment group, compared to the KPD + CEQ-INJ treatment group.
Our results reveal that CEQ-PLGA-MS has the better therapeutic effect than CEQ-INJ for Klebsiella pneumonia lung infections in rats. The vehicle of CEQ-PLGA-MS as the promising alternatives to control the lung infections with the important pathogens.
本研究旨在比较头孢喹肟(CEQ)负载聚乳酸-羟基乙酸共聚物(PLGA)微球(CEQ-PLGA-MS)与 CEQ 注射液(CEQ-INJ)在肺炎克雷伯菌大鼠肺部感染模型中的体内活性。
将 48 只大鼠分为对照组(假手术,无感染和药物治疗)、肺炎克雷伯菌模型组(KPD+生理盐水)、CEQ-PLGA-MS 和 CEQ-INJ 治疗组(KPD+CEQ-PLGA-MS 和 KPD+INJ,分别)。在 KPD+生理盐水组,大鼠感染肺炎克雷伯菌 ATCC 10031。在 KPD+CEQ-PLGA-MS 和 KPD+INJ 组,感染大鼠分别静脉注射 12.5mg/kg 体重的 CEQ-PLGA-MS 和 CEQ-INJ。
与 CEQ-INJ 治疗组相比,CEQ-PLGA-MS 治疗组进一步降低了肺组织中细菌菌落数量(降至 1.94 lg CFU/g)和支气管肺泡灌洗液中炎症细胞因子 TNF-α、IL-1β、IL-6、IL-4 的水平(p<0.05 或 p<0.01),在 48 小时。同样,在 KPD+CEQ-PLGA-MS 治疗组,与 KPD+CEQ-INJ 治疗组相比,在 48 小时时炎症严重程度评分显著降低。
我们的结果表明,CEQ-PLGA-MS 对肺炎克雷伯菌肺部感染的治疗效果优于 CEQ-INJ。CEQ-PLGA-MS 的载体为控制重要病原体引起的肺部感染提供了有前途的替代方案。