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小牛肺表面活性剂在暴露于含有聚合物颗粒的气溶胶后可恢复表面功能。

Calf Lung Surfactant Recovers Surface Functionality After Exposure to Aerosols Containing Polymeric Particles.

作者信息

Farnoud Amir M, Fiegel Jennifer

机构信息

1 Department of Chemical and Biochemical Engineering, The University of Iowa , Iowa City, Iowa.

2 Department of Pharmaceutical Sciences and Experimental Therapeutics, The University of Iowa , Iowa City, Iowa.

出版信息

J Aerosol Med Pulm Drug Deliv. 2016 Feb;29(1):10-23. doi: 10.1089/jamp.2014.1165. Epub 2015 Feb 11.

Abstract

BACKGROUND

Recent studies have shown that colloidal particles can disrupt the interfacial properties of lung surfactant and thus key functional abilities of lung surfactant. However, the mechanisms underlying the interactions between aerosols and surfactant films remain poorly understood, as our ability to expose films to particles via the aerosol route has been limited. The aim of this study was to develop a method to reproducibly apply aerosols with a quantifiable particle dose on lung surfactant films and investigate particle-induced changes to the interfacial properties of the surfactant under conditions that more closely mimic those in vivo.

METHODS

Films of DPPC and Infasurf were exposed to aerosols containing polystyrene particles generated using a Dry Powder Insufflator. The dose of particles deposited on surfactant films was determined via light absorbance. The interfacial properties of the surfactant were studied using a Langmuir-Wilhelmy balance during surfactant compression to film collapse and cycles of surface compression and expansion at a fast cycling rate within a small surface area range.

RESULTS

Exposure of surfactant films to aerosols led to reproducible dosing of particles on the films. In film collapse experiments, particle deposition led to slight changes in collapse surface pressure and surface area of both surfactants. However, longer interaction times between particles and Infasurf films resulted in time-dependent inhibition of surfactant function. When limited to lung relevant surface pressures, particles reduced the maximum surface pressure that could be achieved. This inhibitory effect persisted for all compression-expansion cycles in DPPC, but normal surfactant behavior was restored in Infasurf films after five cycles.

CONCLUSIONS

The observation that Infasurf was able to quickly restore its function after exposure to aerosols under conditions that better mimicked those in vivo suggests that particle-induced surfactant inhibition is unlikely to occur in vivo due to an aerosol exposure.

摘要

背景

近期研究表明,胶体颗粒可破坏肺表面活性剂的界面特性,进而影响肺表面活性剂的关键功能。然而,由于通过气溶胶途径使薄膜暴露于颗粒的能力有限,气溶胶与表面活性剂薄膜之间相互作用的潜在机制仍知之甚少。本研究的目的是开发一种方法,可在肺表面活性剂薄膜上可重复地施加具有可量化颗粒剂量的气溶胶,并在更接近体内条件下研究颗粒引起的表面活性剂界面特性变化。

方法

使用干粉吸入器产生含有聚苯乙烯颗粒的气溶胶,将二棕榈酰磷脂酰胆碱(DPPC)和英孚美(Infasurf)的薄膜暴露于该气溶胶中。通过吸光度测定沉积在表面活性剂薄膜上的颗粒剂量。在表面活性剂压缩至薄膜塌陷以及在小表面积范围内以快速循环速率进行表面压缩和膨胀循环期间,使用Langmuir-Wilhelmy天平研究表面活性剂的界面特性。

结果

将表面活性剂薄膜暴露于气溶胶可导致颗粒在薄膜上的可重复给药。在薄膜塌陷实验中,颗粒沉积导致两种表面活性剂的塌陷表面压力和表面积略有变化。然而,颗粒与英孚美薄膜之间较长的相互作用时间导致表面活性剂功能随时间受到抑制。当限于与肺相关的表面压力时,颗粒降低了可达到的最大表面压力。这种抑制作用在DPPC的所有压缩-膨胀循环中持续存在,但在五个循环后英孚美薄膜恢复了正常的表面活性剂行为。

结论

在更好地模拟体内条件下,英孚美在暴露于气溶胶后能够迅速恢复其功能,这一观察结果表明,由于气溶胶暴露,颗粒诱导的表面活性剂抑制在体内不太可能发生。

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