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“The decrease in the collapse pressure of the monolayer film caused by coated nanoparticles,<br />

in vitro, was associated with an acute pulmonary toxicity in vivo.”<br />

American Association Of Pharmaceutical Sciences • September 2010<br />

Pulmonary Toxicity of Polysorbate-80-coated<br />

Inhalable Nanoparticles; In vitro and In vivo Evaluation<br />

M. H. D. Kamal Al-Hallak, Shirzad Azarmi, Chris Sun, Patrick Lai,<br />

Elmar J. Prenner, Wilson H. Roa, and Raimar Löbenberg<br />

Faculty of Pharmacy and Pharmaceutical Sciences, 3126 Dentistry/Pharmacy Centre<br />

University of Alberta, Edmonton, Alberta T6G 2N8 Canada<br />

Faculty of Pharmacy and Pharmaceutical Sciences, Damascus University, Damascus, Syria<br />

Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran<br />

Department of Biological Sciences, University of Calgary, Calgary, Alberta Canada<br />

Cross Cancer Institute, University of Alberta, Edmonton, Alberta Canada<br />

CONCLUSION<br />

The presented in vitro model for studying the surface pressure-area isotherms is an early screening tool to assess<br />

the biophysical compatibility of selected drug carriers with lung surfactant films. The decrease in the collapse<br />

pressure of the monolayer film caused by coated NPs, in vitro, was associated with an acute pulmonary toxicity<br />

in vivo. This in vivo toxicity was not observed when uncoated nanoparticles were used. Therefore, the dosage<br />

from toxicity of colloidal carriers intended for pulmonary delivery is mainly determined by their final composition<br />

rather than their individual components. More investigations are required to set different cut-off points for<br />

the collapse pressure to correlate them with different stages of pulomary toxicity in vivo. The outcomes of this<br />

study should not be generalized for all surfactants or bi-block polymers. Other surfactants with different hydrophilic-lipophilic<br />

properties might interact differently with lung surfactant films. This method may be useful to<br />

establish upper deposition limits for inhalable dry powders.<br />

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2895437/

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