Henning A, Schneider M, Bur M, Blank F, Gehr P, Lehr C-M
Biopharmaceutics and Pharmaceutical Technology, Saarland University, P.O. Box 151150, 66041 Saarbrücken, Germany.
AAPS PharmSciTech. 2008;9(2):521-7. doi: 10.1208/s12249-008-9072-6. Epub 2008 Apr 2.
Mucociliary clearance (MC) is an important defense mechanism of the respiratory system to eliminate inhaled and possibly noxious particles from the lung. Although the principal mechanics of MC seem to be relatively clear there are still open questions regarding the long-term clearance of particles. Therefore, we have developed a new set-up based on embryonic chicken trachea (ECT) to investigate mucociliary particle clearance in more detail. ECT was placed in an incubation chamber after carbon particles were applied and tracked using optical microscopy. The aim of the study was to validate this model by investigating the impact of temperature, humidity and drugs on particle transport rates. Particles were transported reproducibly along the trachea and clearance velocity (2.39 +/- 0.25) mm/min was found to be in accordance to data reported in literature. Variation in temperature resulted in significantly reduced MC: (0.40 +/- 0.12) mm/min (20 degrees C); (0.42 +/- 0.10) mm/min (45 degrees C). Decreasing humidity (99-60%) had no significant effect on MC, whereas reduction to 20% humidity showed a significant influence on particle clearance. The use of different cilio- and muco-active drugs (propranolol, terbutalin, N-acetylcysteine) resulted in altered MC according to the pharmacological effect of the substances: a concentration dependent decrease of MC was found for Propranolol. From our results we conclude that this model can be employed to investigate MC of particles in more detail. Hence, the model may help to understand and identify decisive physico-chemical parameters for MC and to answer open questions regarding the long-term clearance phenomenon.
黏液纤毛清除(MC)是呼吸系统的一种重要防御机制,可从肺部清除吸入的以及可能有害的颗粒。尽管MC的主要机制似乎相对清晰,但关于颗粒的长期清除仍存在一些未解决的问题。因此,我们开发了一种基于胚胎鸡气管(ECT)的新装置,以更详细地研究黏液纤毛颗粒清除情况。在施加碳颗粒后,将ECT置于培养箱中,并使用光学显微镜进行跟踪。本研究的目的是通过研究温度、湿度和药物对颗粒传输速率的影响来验证该模型。颗粒沿气管可重复传输,清除速度为(2.39±0.25)mm/分钟,与文献报道的数据一致。温度变化导致MC显著降低:(0.40±0.12)mm/分钟(20摄氏度);(0.42±0.10)mm/分钟(45摄氏度)。湿度降低(99 - 60%)对MC没有显著影响,而湿度降至20%对颗粒清除有显著影响。使用不同的纤毛和黏液活性药物(普萘洛尔、特布他林、N - 乙酰半胱氨酸)会根据物质的药理作用导致MC改变:普萘洛尔导致MC呈浓度依赖性降低。从我们的结果可以得出结论,该模型可用于更详细地研究颗粒的MC。因此,该模型可能有助于理解和确定MC的决定性物理化学参数,并回答有关长期清除现象的未解决问题。