Epithelial transport of Noscapine across cell monolayer and influence of absorption enhancers on in vitro permeation and bioavailability: implications for intestinal absorption

摘要

The purpose of this study was to investigate the permeation of Noscapine (Nos) across the Caco-2 and Madin-Darby canine kidney (MDCK) cell monolayers and to evaluate the influence of absorption enhancers on in vitro and in vivo absorption of Nos. The bidirectional transport of Nos was studied in Caco-2 and MDCK cell monolayers at pH 5.0-7.8. The effect of 0.5% w/v chitosan (CH) or Captisol (CP) on Nos permeability was investigated at pH 5.0 and 5.8. The effect of 1-5% w/v of CP on oral bioavailability of Nos (150 mg/kg) was evaluated in Sprague-Dawley rats. The effective permeability coefficients (Peff) of Nos across Caco-2 and MDCK cell monolayers was found to be in the order of pH 5.0>5.8>6.8>7.8. The efflux ratios of P-eff<2 demonstrated that active efflux does not limit the absorption of Nos. The use of CH or CP have shown significant (***, p<0.001) enhancement in Peff of Nos across cell monolayer compared with the control group. The CP (1-5% w/v) based Nos formulations resulted in significant (***, p<0.001) increase in the bioavailability of Nos compared with Nos solution. The use of CP represents viable approach for enhancing the oral bioavailability of Nos and reducing the required dose.