Delivery of rifampicin-PLGA microspheres into alveolar macrophages is promising for treatment of tuberculosis
Delivery of rifampicin-PLGA microspheres into alveolar macrophages is promising for treatment of tuberculosis
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DOI：
10.1016/j.jconrel.2009.11.020
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发表时间：
2010-03-19
影响因子：
10.8
通讯作者：
Terada, Hiroshi
中科院分区：
文献类型：
--
作者：
Hirota, Keiji;Hasegawa, Taizo;Terada, Hiroshi
将抗结核药物利福平（rifampicin）聚乳酸-羟基乙酸共聚物（PLGA）微球（RFP-PLGA-MS）吸入肺泡巨噬细胞（M phi），可作为治疗结核病的一种有效给药系统。为了检验这种可能性，我们研究了（1）RFP-PLGA MS对牛分枝杆菌卡介苗（BCG）感染的大鼠肺泡M phi NR 8383细胞的杀菌作用，和（2）通过RFP-PLGA MS的摄取在这些细胞中诱导的生化事件的变化。通过含有0.25和2.50 μ g RFP/μ l的RFP-PLGA MS输入到M φ s中的细胞内RFP的量。mL，分别是5.00 μ g/mL REP溶液的2倍和10倍以上;培养7天后，MS对M phi细胞内BCG的杀菌作用强于5.00 μ g RFP/mL溶液。RFP-PLGA MS对M phi细胞活力影响不大，而聚苯乙烯乳胶（PSL）MS则显著降低M phi细胞活力。RFP-PLGA MS不刺激M phi细胞产生肿瘤坏死因子-α（TNF-α）、一氧化氮、白细胞介素-10（IL-10）和转化生长因子-β 1（TGF-β 1），而PSL MS刺激除IL-10外的所有这些介质。我们得出结论，RFP-PLGA MS是生物安全的微球，由于其“沉默”的性质时，采取M phi细胞，他们是有前途的肺吸入治疗结核。(C)2009 Elsevier B. V.保留所有权利。
Inhalation delivery of poly(lactic-co-glycolic) acid (PLGA) microspheres (MS) loaded with the anti-tuberculosis agent rifampicin (RFP-PLGA MS) to alveolar macrophage (M phi) cells could be an effective drug delivery system for the treatment of tuberculosis. To examine this possibility, we studied (1) the bactericidal effect of RFP-PLGA MS on Mycobacterium bovis Bacillus Calmette-Guerin (BCG)-infected rat alveolar M phi NR8383 cells, and (2) changes in the biochemical events induced in these cells by the uptake of RFP-PLGA MS. The amount of intracellular RFP imported into the M phi s by RFP-PLGA MS containing 0.25 and 2.50 mu g RFP/mL was more than twice and ten times, respectively, than that attained with 5.00 mu g/mL of REP solution: and the MS exerted more potent bactericidal effect on BCG inside M phi cells than 5.00 mu g RFP/mL solution after incubation for 7 days. RFP-PLGA MS little affected the viability of M phi cells, whereas the polystyrene latex (PSL) MS used as a reference decreased it significantly. RFP-PLGA MS did not stimulate the production of tumor necrosis factor-alpha (TNF-alpha), nitric oxide, interleukin-10 (IL-10), and transforming growth factor-beta 1 (TGF-beta 1) by the M phi cells, whereas PSL MS stimulated all of these mediators except IL-10. We conclude that RFP-PLGA MS are bio-safe microspheres due to their "silent" nature when taken into M phi cells and that they are promising for the treatment of tuberculosis by pulmonary inhalation. (C) 2009 Elsevier B.V. All rights reserved.