Montmorillonite-surfactant hybrid particles for modulating intestinal P-glycoprotein-mediated transport

Abstract

In the small intestine, P-glycoprotein (P-gp) may limit the permeability of its substrates, which lead to reduced oral absorption. To circumvent the effect of P-gp, a nanocomposite material termed montmorillonite-surfactant hybrid particles was developed. The particles consisted of montmorillonite, the P-gp-inhibiting, nonionic surfactant, polysorbate 20, and the P-gp substrate, digoxin. The present study aimed to investigate if montmorillonite-surfactant hybrid particles could modulate the absorption of digoxin in vivo. Montmorillonite-surfactant hybrid particles were prepared by lyophilising an aqueous suspension of the constituents. Scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and powder X-ray diffraction (PXRD) revealed an altered surface morphology, decreased water content, and intercalation of polysorbate 20 between montmorillonite layers. The particles were administered orally to Sprague Dawley rats, and digoxin was quantified by liquid chromatography-tandem mass spectrometry. Control digoxin-containing montmorillonite decreased the exposure of digoxin. In contrast, montmorillonite-surfactant hybrid particles increased AUC and Cmax by 31 and 91 %, respectively, compared to digoxin in solution. It was hypothesised that montmorillonite-surfactant hybrid particles increased digoxin exposure by forming mucosalocalised elevated concentrations of polysorbate 20 and digoxin, which enhanced the inhibitory effect of polysorbate 20 on P-gp.

Oral etoposide and zosuquidar bioavailability in rats: Effect of co-administration and in vitro-in vivo correlation of P-glycoprotein inhibition

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Polysorbate-Based Drug Formulations for Brain-Targeted Drug Delivery and Anticancer Therapy

“…To inhibit the effect of P-gp, a clay-based nanocomposite using montmorillonite and PS 20 was developed [50]. The particles consisted of montmorillonite, the nonionic surfactant PS 20, and the P-gp substrate digoxin.…”

Two different routes to prepare porous biodegradable composite membranes containing nanoclay

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