title: Enhancing effect of hydroxypropyl-β-cyclodextrin on the intestinal absorption process of genipin.
abstract: The purpose of this work is to investigate the effect of the genipin/hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complex on the intestinal absorption of genipin and identify its mechanism of action. The phase solubility profile was classified as A(L) type, indicating the formulation of a 1:1 stoichiometry inclusion complex. Fourier transform infrared spectroscopy, Differential scanning calorimetry, X-ray powder diffractometry, and (1)H nuclear magnetic resonance (NMR) and two-dimensional (2D) (1)H rotating-frame Overhauser enhancement (ROESY) NMR spectroscopies further confirmed the formulation of the inclusion complex with superior dissolution properties than the drug alone. The results of single-pass intestinal perfusion showed that the intestinal absorption of genipin was affected by P-glycoprotein (Pgp). The absorption rate and permeability value of the inclusion complex were significantly higher than the free drug, suggesting that its enhancing effect was involved in its solubilizing effect and Pgp inhibitory effect. The mechanisms of HP-β-CD on Pgp inhibition were demonstrated by restraining the Pgp ATPase activity rather than changing the fluidity of the cell membrane.
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, People's Republic of China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.forename: Fan-Cui
authors.initials: FC
authors.lastname: Meng
authors.forename: Yuan-Lu
authors.initials: YL
authors.lastname: Cui
authors.forename: Yan-Fei
authors.initials: YF
authors.lastname: Song
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D000818:Animals; D002626:Chemistry, Pharmaceutical; D002756:Cholagogues and Choleretics / Q000493:pharmacokinetics; D007408:Intestinal Absorption / Q000187:drug effects*; D057889:Iridoid Glycosides / Q000737:chemistry / Q000493:pharmacokinetics*; D039823:Iridoids; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002756:Cholagogues and Choleretics; D057889:Iridoid Glycosides; D039823:Iridoids; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C007834:genipin