Title: Mechanistic appraisal of the effects of some protease inhibitors on ciliary beat frequency in a sequential cell culture system of human nasal epithelium
Authors: Remigius, Uchenna Agu ×
Jorissen, Mark
Willems, Tom
Kinget, Renaat
Verbeke, Norbert #
Issue Date: May-2003
Series Title: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft für Pharmazeutische Verfahrenstechnik e.V vol:55 issue:3 pages:283-9
Abstract: The aim of this study was to investigate the suitability of a sequential monolayer-suspension culture system as a model to screen subacute effects of drug excipients on ciliary beat frequency (CBF). The CBF of the cultured cells was measured by computerized microscope photometry. Protease inhibitors (puromycin, bestatin, bacitracin, actinonin and thiomersal) were used as model compounds and the mechanisms of ciliary inhibition were investigated by probing the involvement of arachidonic acid metabolism, guanylate cyclase (cGMP), protein kinase C (PKC) and adenosinetriphosphate (ATP) inhibition. Bestatin concentration-dependently reduced CBF by inhibiting arachidonic acid metabolism, cGMP, PKC and endogenous ATP consumption. Thiomersal and DMSO used for dissolving actinonin reduced CBF (P<0.05) via a non-specific mechanism. Bacitracin (8 mM) and puromycin (135 mM) had no effect on CBF after acute exposure (15-30 min) (P>0.05), but significantly reduced the CBF by approximately 15.0% following daily 15-min exposure for 1 week. This study shows that (i) sequential monolayer-suspension culture system is a valid model to screen both acute and subacute effects of drug excipients on CBF; and (ii) bacitracin, puromycin and actinonin are more cilio-compatible than bestatin and thiomersal and as such are more potentially useful nasal absorption enhancer from ciliotoxicity perspective.
ISSN: 0939-6411
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Drug Delivery and Disposition
Research Group Experimental Oto-rhino-laryngology
× corresponding author
# (joint) last author

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