Evaluation of dosing regimen of respirable rifampicin biodegradable microspheres in the treatment of tuberculosis in the guinea pig
Evaluation of dosing regimen of respirable rifampicin biodegradable microspheres in the treatment of tuberculosis in the guinea pig
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DOI：
10.1093/jac/dkl369
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发表时间：
2006-11-01
影响因子：
5.2
通讯作者：
Hickey, A. J.
中科院分区：
文献类型：
--
作者：
Garcia-Contreras, L.;Sethuraman, V.;Hickey, A. J.
目的：比较载利福平聚合物微球（RPLGA）对感染结核分枝杆菌（H37Rv）的豚鼠的疗效，并与日剂量雾化利福平混悬液进行比较。方法：采用RPLGA、PLGA微球或利福平微细悬浮气雾剂对感染动物进行多剂量或单剂量治疗。为了与微球混悬液治疗进行比较，其他组接受每日剂量的利福平混悬液治疗20 （20- rif）和10 （10- rif）天。结果：药物和聚合物处理多剂量组动物肺湿重明显低于未处理组。药物微球处理动物脾脏湿重和活菌计数明显低于其他各组。在单利福平混悬液的多剂量研究中，10-RIF和20-RIF处理动物的湿肺重量比对照组小得多。同样，10-RIF和20-RIF治疗的动物湿脾重量比对照组小得多，与炎症减轻一致。20-RIF组小鼠脾脏VBC明显小于对照组。单剂量组间肺VBC差异无统计学意义。然而，观察到与湿重相似的趋势。结论：雾化RPLGA减少了大多数结核病（TB）感染。这些研究进一步证明了吸入气雾剂治疗结核病的潜力。然而，需要进一步的研究来阐明潜在的作用机制并优化这种给药途径。
Objectives: The efficacy of rifampicin-loaded polymeric microspheres (RPLGA) delivered to guinea pigs infected with Mycobacterium tuberculosis (H37Rv) was compared with a daily dose of nebulized rifampicin suspension.Methods: Aerosol-infected animals were subjected to multiple dose or single dose treatment with RPLGA, PLGA microspheres or micronized rifampicin suspension aerosols. For comparison with treatment with suspensions of microspheres, additional groups received daily doses of rifampicin-only suspensions for 20 (20-RIF) and 10 (10-RIF) days.Results: Drug and polymer treated multiple dose groups exhibited significantly lower wet lung weights than untreated animals. Spleen wet weights and viable bacterial counts (VBCs) were much lower for drug microsphere treated animals than for all other groups. In multiple dose studies with rifampicin-only suspensions, wet lung weights for 10-RIF and 20-RIF treated animals were much smaller than controls. Likewise, wet spleen weights of 10-RIF and 20-RIF treated animals were much smaller than controls, consistent with reduced inflammation. Spleen VBC of 20-RIF treated animals was much smaller than controls. No statistical differences were observed in the lung VBC among single dose groups. However, a trend similar to that of the wet weights was observed.Conclusions: Aerosolized RPLGA reduced most measures of tuberculosis (TB) infection. These studies are further evidence for the potential of inhaled aerosol therapy for the treatment of TB. However, additional studies are required to elucidate underlying mechanisms of action and optimize this route of drug delivery.