利福平聚乳酸-羟基乙酸共聚物纳米粒雾化吸入给药肺靶向性研究

Targeted Study of Rifampicin Polylactic Acid/Glycolic Acid Copolymer Nanoparticles Aerosol Inhalation in Lung

目的研究利福平聚乳酸-羟基乙酸共聚物纳米粒雾化吸入给药的肺靶向性。方法分别将利福平聚乳酸-羟基乙酸共聚物纳米粒混悬液(RFP-PLGA-NPs)和利福平注射液(RFP-Sol)以雾化吸入方式给予SD大鼠,在不同时间点测定利福平在大鼠肺组织中的浓度,计算相应药动学参数,比较2种制剂在肺组织中药动学过程,并评价靶向性。结果 RFP-Sol和RFP-PLGA-NPs的Tmax分别为(1.50±0.01)h和(2.00±0.08)h,Cmax分别为(0.83±0.07)mg.L 1和(5.02±0.05)mg.L 1,AUC0→∞分别为(6.24±0.24)mg.h.L 1和(35.80±6.34)mg.h.L 1,CL分别为(4.801±0.18)L.h 1.kg 1和(0.85±0.15)L.h 1.kg 1。通过对re和Ce等靶向性指标进行分析,RFP-PLGA-NPs在肺组织中的re和Ce均>1。结论与RFP-Sol相比,RFP-PLGA-NPs经雾化吸入给药后,明显提高了肺组织中药物的分布并且延缓消除,有显著的缓释性,从而降低药物对全身的不良反应,提高对肺结核的治疗作用。

OBJECTIVE To investigate the targeted character of rifampicin polylactic acid/glycolic acid copolymer nanoparticles in lung after nebulized inhalation in rats.METHODS The rifampicin nanoparticles suspension（RFP-PLGA-NPs） and rifampicin suspension（RFP-Sol） were given to SD rats by nebulized inhalation,respectively.The concentrations of two formulations in lung at different time after nebulized inhalation were analyzed.Further more,their pharmacokinetic parameters were compared,and the targeted character was evaluated.RESULTS T max of RFP-Sol and RFP-PLGA-NPs were（1.50±0.01） hand（2.00±0.08）h,C max were（0.83±0.07）mg.L 1 and（5.02±0.05）mg.L 1,AUC 0→∞ were（6.24±0.24）mg.h.L 1 and（35.80±6.34） mg.h.L 1,CL were（4.81±0.18） L.h 1.kg 1 and（0.85±0.15）L.h 1.kg 1,respectively.Moreover,C e and r e of the two formulations in lung were analysed,which exceeded 1.CONCLUSION Compared with RFP-Sol,the nanoparticles after nebulized inhalation might elevate their distribution and slow their elimination in lung,and decrease the drug adverse reaction in rats,so as to improve the treatment efficacy of pulmonary tuberculosis.