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Small Airway Absorption and Microdosimetry of Inhaled Corticosteroid Particles after Deposition

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Abstract

Purpose

To predict the cellular-level epithelial absorbed dose from deposited inhaled corticosteroid (ICS) particles in a model of an expanding and contracting small airway segment for different particle forms.

Methods

A computational fluid dynamics (CFD)-based model of drug dissolution, absorption and clearance occurring in the surface liquid of a representative small airway generation (G13) was developed and used to evaluate epithelial dose for the same deposited drug mass of conventional microparticles, nanoaggregates and a true nanoaerosol. The ICS medications considered were budesonide (BD) and fluticasone propionate (FP). Within G13, total epithelial absorption efficiency (AE) and dose uniformity (microdosimetry) were evaluated.

Results

Conventional microparticles resulted in very poor AE of FP (0.37%) and highly nonuniform epithelial absorption, such that <5% of cells received drug. Nanoaggregates improved AE of FP by a factor of 57-fold and improved dose delivery to reach approximately 40% of epithelial cells. True nanoaerosol resulted in near 100% AE for both drugs and more uniform drug delivery to all cells.

Conclusions

Current ICS therapies are absorbed by respiratory epithelial cells in a highly nonuniform manner that may partially explain poor clinical performance in the small airways. Both nanoaggregates and nanoaerosols can significantly improve ICS absorption efficiency and uniformity.

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Acknowledgments and Disclosures

Alex Rygg is gratefully acknowledged for developing a previous version of the CFD-based DAC model while working as a postdoc in the Longest Lab at VCU. This study was supported by Award U01 FD004570 from the US FDA. The content is solely the responsibility of the authors and does not necessarily represent the official views of the US FDA. The authors are developing techniques for pharmaceutical nanoparticle production and improved small airway targeting, which if licensed, may provide a future financial interest.

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  1. Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, 401 West Main Street, Virginia, 23284-3015, USA

    P. Worth Longest

  2. Department of Pharmaceutics, Virginia Commonwealth University, Richmond, Virginia, USA

    P. Worth Longest & Michael Hindle

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Longest, P.W., Hindle, M. Small Airway Absorption and Microdosimetry of Inhaled Corticosteroid Particles after Deposition. Pharm Res 34, 2049–2065 (2017). https://doi.org/10.1007/s11095-017-2210-7

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