Hypersecretion of mucus is associated with impaired mucociliary clearance that can influence the retention of active pharmaceutical ingredients in the airway but is also linked with recurrent airway disease. Therefore, the effect on mucin secretion of a range of ingredients used in solutions delivered to the nose and lung was studied. Mucin secretion from explants of ovine epithelium was quantified using an enzyme-linked lectin assay (ELLA) or sandwich ELLA depending on the compatibility of the ingredients with the assay. Benzalkonium chloride (0.015% w/w), Methocel™ E50 premium LV (1.0% w/w), propylene glycol (1.5% w/w), potassium sorbate + propylene glycol (0.3% w/w + 1.5% w/w) and polysorbate 80 (0.025% w/w), used at common working concentrations, all increased the secretion of mucin from the explants (P < 0.05). Ethylenediamine tetraacetic acid-disodium salt (EDTA) (0.015% w/w), Avicel® RC591 (1.5% w/w), fluticasone furoate (0.0004% w/w, concentration in solution) and dimethyl sulfoxide (DMSO) (0.2% w/w) did not affect mucin secretion. Compounds increasing mucin secretion could alter the rate of mucociliary clearance and the mucus could provide a barrier to drug absorption. This could predispose patients to disease and affect the activity of delivered drugs, decreasing or increasing their clinical efficacy.
|Journal||International Journal of Pharmaceutics|
|Publication status||Published - 28 Aug 2021|
Bibliographical noteFunding Information:
This work was supported by the University of Brighton and GlaxoSmithKline UK (GlaxoSmithKline, David Jack Centre for Research and Development), Park Road, Ware, Herts, SG12 0DP, UK).
- Avicel® RC591
- Benzalkonium chloride
- Dimethyl sulfoxide (DMSO)
- Enzyme-linked lectin assay
- Ethylenediamine tetraacetic acid-disodium salt (EDTA)
- Fluticasone furoate
- Methocel™ E50 premium LV
- Nasal drug delivery
- Polysorbate 80 (Tween 80)
- Potassium sorbate
- Propylene glycol