Prediction of acute inhalation toxicity using in vitro lung surfactant inhibition

Sørli, Jorid B.

doi:10.14573/altex.1705181s

Cited by 2 publications

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Bile salt enhancers for inhalation: Correlation between in vitro and in vivo lung effects

Sørli

Sivars

Silva

et al. 2018

International Journal of Pharmaceutics

View full text Add to dashboard Cite

The lungs have potential as a means of systemic drug delivery of macromolecules. Systemic delivery requires crossing of the air-blood barrier, however with molecular size-dependent limitations in lung absorption of large molecules. Systemic availability after inhalation can be improved by absorption enhancers, such as bile salts. Enhancers may potentially interfere with the different constituents of the lungs, e.g. the lung surfactant lining the alveoli or the lung epithelium. We used two in vitro models to investigate the potential effects of bile salts on lung surfactant function (with the constrained drop surfactometer) and on the epithelium in the proximal airways (with the MucilAir™ cell system), respectively. In addition, we measured direct effects on respiration in mice inhaling bile salt aerosols. The bile salts inhibited lung surfactant function at different dose levels, however they did not affect the integrity of ciliated cells at the tested doses. Furthermore, the bile salt aerosols induced changes in the breathing pattern of mice indicative of pulmonary irritation. The bile salts were ranked according to potency in vitro for surfactant function disruption and in vivo for induction of pulmonary irritation. The ranking was the same, suggesting a correlation between the interference with lung surfactant and the respiratory response.

show abstract

Bile salt enhancers for inhalation: Correlation between in vitro and in vivo lung effects

Sørli

Sivars

Silva

et al. 2018

International Journal of Pharmaceutics

View full text Add to dashboard Cite

show abstract

Experiments and modelling of pulmonary surfactant disruption by aerosolised compounds

Barlow,

Sengupta,

Baltazar

et al. 2024

Preprint

View full text Add to dashboard Cite

Within the deep lung, pulmonary surfactant coats the air-liquid interface at the surface of the alveoli. This complex mixture of amphiphilic molecules and proteins modifies the surface tension and mechanical properties of this interface to assist with breathing. In this study, we examine the effects on pulmonary surfactant function by two industrially used compounds composing surfactants and polymers. Using an experimental method previously developed to imitate the in vivo exposure in the alveoli, we quantify the change in the dilational rheology of the pulmonary surfactant due to the introduction of two widely used chemicals; Benzalkonium Chloride (BAC) and Polyhexamethylene Biguanide (PHMB). We observe that these chemicals alter the dilational rheology of the surfactant monolayer. Using a mechanistic theory, we are able to semi-quantitatively model the changes induced by the introduction of these compounds to the pulmonary surfactant.

show abstract

Prediction of acute inhalation toxicity using in vitro lung surfactant inhibition

Cited by 2 publications

References 25 publications

Bile salt enhancers for inhalation: Correlation between in vitro and in vivo lung effects

Bile salt enhancers for inhalation: Correlation between in vitro and in vivo lung effects

Experiments and modelling of pulmonary surfactant disruption by aerosolised compounds

Contact Info

Product

Resources

About