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

关键词:  利福平  纳米粒  聚乳酸-羟基乙酸共聚物  雾化给药  肺靶向

Key words:  rifampicin  nanoparticles  polylactic acid/glycolic acid copolymer  nebulized inhalation  lung targeting

摘要:

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T_max分别为(1.50±0.01)h和(2.00±0.08)h，C_max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r_e和C_e等靶向性指标进行分析，RFP-PLGA-NPs在肺组织中的r_e和C_e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。

Abstract:

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, AUC₀→∞ 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.