Abstract
Nonionic surfactants commonly used in pharmaceutical formulations may have P-glycoprotein (P-gp) inhibiting and/or permeation enhancing effects. The present work aims to distinguish these effects and assess the degree of cellular recovery after multiple exposures to nonionic surfactants. The investigated surfactants were polysorbates (PS): PS20, PS40, PS60, PS65, PS80 and PS85; monosaccharide-based: lauroyl methyl glucamide and n-nonyl-β-D-glucopyranoside; or disaccharide-based: lauryl-β-D-maltoside and trehalose 6-laurate. Bi-directional permeability studies of digoxin and mannitol, and calcein-AM efflux assay were performed in cell cultures. Cellular recovery was evaluated by continuous measurements of transepithelial electrical resistance (TEER) in Caco-2 cell monolayers. Polysorbates with one fatty acid chain decreased the efflux of digoxin through P-gp inhibition in MDCKII MDR1 cells. Mono- and di-saccharide-based surfactants, in a dose dependent manner, enhanced digoxin absorptive permeability without decreasing the secretory permeability in Caco-2 cells, suggesting that the surfactants had a transcellular permeation enhancing effect. Caco-2 cell monolayers recovered to different degrees of 60–100% of the initial TEER values. Calcein-AM assay was found to be non-predictive to surfactants influence on digoxin permeability across cell monolayers. In conclusion, these results may assist, in a mechanism-based, selection of suitable surfactants for formulating oral dosage forms to enhance the absorption of low bioavailable P-gp substrates.
Originalsprog | Engelsk |
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Tidsskrift | International Journal of Pharmaceutics |
Vol/bind | 551 |
Udgave nummer | 1-2 |
Sider (fra-til) | 270-280 |
ISSN | 0378-5173 |
DOI | |
Status | Udgivet - nov. 2018 |
Emneord
- Nonionic surfactant
- P-glycoprotein
- Digoxin
- Calcein-AM
- Caco-2
- MDCKII MDR1
- TEER