Absorption mechanism of paeonol nanoemulsion using in vitro intestinal cell models

doi:10.5246/jcps.2019.03.017

Abstract

Abstract:

The use of nanoemulsion has improved the bioavailability of paeonol, and that is mainly because of the P-glycoprotein(P-gp)-mediated efflux described in our previous study. However, other mechanisms involved in the intestinal absorption of paeonol nanoemulsion are still unknown. Therefore, we aimed to investigate additional paeonol nanoemulsion absorption mechanisms. By establishing the Caco-2 cells model and the follicle-associated epithelium (FAE) model, uptake studies and bidirectional transport of paeonol nanoemulsion in the presence of different efflux inhibitors were conducted to observe its intake and transport. The paracellular pathway was evaluated by fluorescent staining of Occludin, and the expressions of efflux proteins and tight junction proteins were detected by Western blotting analysis. In this study, we found that nanoemulsion improved the absorption of paeonol by increasing its uptake across the Caco-2 and FAE cells and by reducing the expressions of efflux proteins. In addition, paeonol nanoemulsion had no effect on the opening of tight junctions. The results showed that the absorption of paeonol nanoemulsion occurred by passive diffusion in the Caco-2 cell model and by endocytosis in the FAE model, which was related to multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP) efflux. Paeonol nanoemulsion significantly increased the absorption of the drug in intestinal cells, which was possibly related to the increase in intestinal cell uptake, inhibited expressions of efflux protein and reduction of drug efflux.

Key words: Paeonol nanoemulsion, Absorption mechanism, Uptake, Transport

CLC Number:

R962

Supporting:

Yi Ouyang, Jing Zhang, Hongfei Wu, Min Dai. Absorption mechanism of paeonol nanoemulsion using in vitro intestinal cell models[J]. Journal of Chinese Pharmaceutical Sciences, 2019, 28(3): 174-185.

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