Mucociliary clearance of micro- and nanoparticles is independent of size, shape and charge--an ex vivo and in silico approach.
The fate of inhaled particles after deposition onto the pulmonary mucosa is far from being solved, in particular with respect to mucociliary clearance and mucus penetration. Due to the fact that these phenomena govern pulmonary residence time and thus bioavailability, they are highly relevant for any kind of controlled release formulation delivered via that route. This study applies ex vivo and in silico approaches to investigate the dependency of muciliary clearance of micro-, submicrometer and nanoparticles on size, shape, charge and surface chemistry of such particles. In addition, measurement of mucociliary clearance of different particles also provided information about their penetration into mucus. Surprisingly, no significant differences in mucociliary clearance could be found for any type of particle under investigation. As revealed by computational modeling, particle penetration into the mucus gel layer was negligible at least within the time frame allowed by horizontal mucus transport. These data suggest that the observed lack of difference in mucociliary clearance is caused by the lack of immediate penetration of deposited aerosol particles through the mucus blanket.
Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbruecken, Germany. j.kirch@mx.uni-saarland.de
Julian
J
Kirch
Marco
M
Guenther
Nishit
N
Doshi
Ulrich F
UF
Schaefer
Marc
M
Schneider
Samir
S
Mitragotri
Claus-Michael
CM
Lehr
D000818:Animals; D002642:Chick Embryo; D003198:Computer Simulation; D008168:Lung / Q000378:metabolism*; D008954:Models, Biological; D009079:Mucociliary Clearance; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D011094:Polyethyleneimine / Q000737:chemistry / Q000378:metabolism; D011137:Polystyrenes / Q000737:chemistry / Q000378:metabolism; D013499:Surface Properties
D011137:Polystyrenes; D011094:Polyethyleneimine