Potential of a novel self nanoemulsifying carrier system to overcome P-glycoprotein mediated efflux of etoposide: In vitro and ex vivo investigations

The oral absorption of etoposide is mainly limited by its active efflux out of the cells by P-glycoprotein (P-gp) and metabolized by cytochrome P450. Therefore, an attempt was aimed to investigate the effect of etoposide-loaded self-nanoemulsifying drug delivery system (SNEDDS) on the absorption of etoposide. The transport of SNE3 formulation across rat intestine was significantly (p < 0.001) higher than that of drug solution alone as well as in presence of verapamil, used as P-gp inhibitor. Results of fluorescence activating cell sorting assay showed a 61.3 ± 2.56% intracellular uptake of fluorescence marker Rhodamine B loaded in SNEDDS while plain Rhodamine B solution showed only a 15.3 ± 1.62% uptake. Confocal laser scanning microscopy study showed significantly higher penetration i.e., 83.71 μm across the GI membrane as compared to plain Rhodamine B solution which showed penetration up to 21.67 μm. Mechanism of P-gp inhibition was confirmed by measuring ATPase activity in the DC-3F/ADX cell model. Moreover, histopathology revealed that epithelial membrane of rat intestine treated with SNE3 was free of abrasion and atrophy. The aforementioned results suggest that the inhibitory effect of SNEDDS on the activity of both P-gp and cytochrome P450 may enhance the oral absorption of etoposide.

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