title: Release characteristics of endogenous constituents by exposure of small intestine to modified beta-cyclodextrins.
abstract: The aim of the present research is to characterize the leakage of intestinal constituents induced by beta-cyclodextrin (beta-CyD) derivatives using an in situ perfusion and an in vitro everted sac. The efficacy of 6-O-alpha-D-glucosyl (G1)- and 6-O-alpha-D-maltosyl (G2)-beta-CyDs as oral carriers was also compared with that of 2-hydroxypropyl-(HP1; average molar degree of substitution, 0.9) and 2,6-di-O-methyl (DM)-beta-CyDs. In the in situ studies, phenol red (PR) penetration and the release profiles of intestinal constituents for G2-beta-CyD were fairly close to those for HP1-beta-CyD. However, the ability of G2-beta-CyD to include cholesterol was greater than that of HP1-beta-CyD. To characterize the release of intestinal constituents induced by modified beta-CyDs, the capability of including cholesterol was held constant between DM- and branched beta-CyDs. The everted sac study showed that the amount of DM-beta-CyD transferred to the serosal side was not significantly different from the branched beta-CyDs. On the serosal side, the amount of cholesterols released was approximately 3 times higher for DM-beta-CyD than for the branched beta-CyDs at 60 min. The cumulative amounts of cholesterols for DM-beta-CyD increased approximately 6 times at 60 min compared with at 30 min, predominating over the leakage (average 2.6-fold) on the mucosal side. In contrast, the exposure of the branched beta-CyDs resulted in an insignificant increase over the period of this experiment. The present study suggests that permeable beta-CyD derivatives play an important role in the leakage of intestinal components. G2-beta-CyD is preferably recommended as a drug solubilizer in oral formulations as well as HP1-beta-CyD, based on the lower release of intestinal constituents.
authors.affiliation: Faculty of Pharmaceutical Sciences, Kinki University, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tanino
authors.forename: T
authors.initials: T
authors.lastname: Ogiso
authors.forename: M
authors.initials: M
authors.lastname: Iwaki
authors.forename: T
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: K
authors.initials: K
authors.lastname: Kakehi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002273:Carcinogens / Q000737:chemistry / Q000494:pharmacology*; D002784:Cholesterol / Q000378:metabolism; D003505:Cyclodextrins / Q000737:chemistry / Q000494:pharmacology*; D007202:Indicators and Reagents / Q000493:pharmacokinetics; D007408:Intestinal Absorption / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D010637:Phenolsulfonphthalein / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D047392:beta-Cyclodextrins
chemical_list: D002273:Carcinogens; D003505:Cyclodextrins; D007202:Indicators and Reagents; D047392:beta-Cyclodextrins; D002784:Cholesterol; D010637:Phenolsulfonphthalein; C031215:betadex