Advanced in vitro exposure systems.

A Proposed In Vitro Method to Assess Effects of Inhaled Particles on Lung Surfactant Function

15. Mar. 2016

DOI: 10.1165/rcmb.2015-0294MA

Jorid B. Sørli1, Emilie Da Silva1, Per Bäckman2, Marcus Levin1, Birthe L. Thomsen1, Ismo K. Koponen1, and Søren T. Larsen1
1The National Research Centre for the Working Environment, Copenhagen, Denmark
2AstraZeneca, Mölndal, Sweden

This study has demonstrated that the modified CDS, a novel method that mimics the conditions for the lung surfactant, is a useful bioassay to assess the acute effects of dry powder aerosols on the lung. The in vitro method, based on the constrained drop surfactometer, different Turbuhaler as well as empty Turbuhaler filled with albumin or lactose were tested. A quartz crystal microbalance was fitted in the chamber to estimate the dose of the deposited particles.


Abstract
The lung surfactant (LS) lining is a thin liquid film covering the air–liquid interface of the respiratory tract. LS reduces surface tension, enabling lung surface expansion and contraction with minimal work during respiration. Disruption of surface tension is believed to play a key role in severe lung conditions. Inhalation of aerosols that interfere with the LS may induce a toxic response and, as a part of the safety assessment of chemicals and inhaled medicines, it may be relevant to study their impact on LS function. Here, we present a novel in vitro method, based on the constrained drop surfactometer, to study LS functionality after aerosol exposure. The applicability of the method was investigated using three inhaled asthma medicines, micronized lactose, a pharmaceutical excipient used in inhaled medication, and micronized albumin, a known inhibitor of surfactant function. The surfactometer was modified to allow particles mixed in air to flow through the chamber holding the surfactant drop. The deposited dose was measured with a custom-built quartz crystal microbalance. The alterations allowed the study of continuously increasing quantified doses of particles, allowing determination of the dose of particles that affects the LS function. The tested pharmaceuticals did not inhibit the function of a model LS even at extreme doses—neither did lactose. Micronized albumin, however, impaired surfactant function. The method can discriminate between safe inhaled aerosols—as exemplified by the approved inhaled medicines and the pharmaceutical excipient lactose—and albumin known to impair lung functionality by inhibiting LS function.

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