Effects of β-cyclodextrin on the intestinal absorption of berberine hydrochloride, a P-glycoprotein substrate

The major objective of this work is to investigate the enhancing effect of beta-cyclodextrin on the intestinal absorption of berberine hydrochloride, a P-glycoprotein (Pgp) substrate. The inclusion complexation behavior of BBH with beta-CD was investigated by phase-solubility diagram, Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray powder diffractometry, NMR spectroscopy, and molecular modeling studies. Results indicated that the 1,3-benzodioxole of BBH was included into the cavity of beta-CD to form an inclusion complex which exhibited higher dissolution rate than BBH in vitro. The intestinal absorption of the inclusion complex in rats was significantly higher than the free drug due to its solubilizing effect and Pgp modulatory activity. The mechanisms of beta-CD on Pgp modulation were demonstrated by modifying the Pgp ATPase activity, the Pgp mRNA level and the Pgp expression. (C) 2013 Elsevier B.V. All rights reserved.