P Worth Longest1,2, Michael Hindle3. 1. Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, 401 West Main Street, Virginia, 23284-3015, USA. pwlongest@vcu.edu. 2. Department of Pharmaceutics, Virginia Commonwealth University, Richmond, Virginia, USA. pwlongest@vcu.edu. 3. Department of Pharmaceutics, Virginia Commonwealth University, Richmond, Virginia, USA.
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.
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.
Authors: M Berry; B Hargadon; A Morgan; M Shelley; J Richter; D Shaw; R H Green; C Brightling; A J Wardlaw; I D Pavord Journal: Eur Respir J Date: 2005-06 Impact factor: 16.671
Authors: Richard A Corley; Senthil Kabilan; Andrew P Kuprat; James P Carson; Kevin R Minard; Richard E Jacob; Charles Timchalk; Robb Glenny; Sudhakar Pipavath; Timothy Cox; Christopher D Wallis; Richard F Larson; Michelle V Fanucchi; Edward M Postlethwait; Daniel R Einstein Journal: Toxicol Sci Date: 2012-05-12 Impact factor: 4.849
Authors: P Worth Longest; Karl Bass; Rabijit Dutta; Vijaya Rani; Morgan L Thomas; Ahmad El-Achwah; Michael Hindle Journal: Expert Opin Drug Deliv Date: 2018-12-10 Impact factor: 6.648