6-O-alpha-(4-O-alpha-D-glucuronyl)-D-glucosyl-beta-cyclodextrin: solubilizing ability and some cellular effects.
Some physicochemical and biopharmaceutical properties of a new branched cyclodextrin, 6-O-alpha-(4-O-alpha-D-glucuronyl)-D-glucosyl-beta-cyclodextrin (GUG-beta-CyD), were investigated. The interaction of GUG-beta-CyD with drugs was studied by spectroscopic and solubility methods, and compared with those of parent beta-CyD and 6-O-alpha-maltosyl-beta-CyD (G(2)-beta-CyD). The hemolytic activity of GUG-beta-CyD on rabbit erythrocytes was lower than those of beta-CyD and G(2)-beta-CyD. GUG-beta-CyD and G(2)-beta-CyD showed negligible cytotoxicity on Caco-2 cells up to at least 0.1 M. The inclusion ability of GUG-beta-CyD to neutral and acidic drugs was comparable to or slightly smaller than those of beta-CyD and G(2)-beta-CyD, probably because of a steric hindrance of the branched sugar. On the other hand, GUG-beta-CyD showed greater affinity for the basic drugs, compared with beta-CyD and G(2)-beta-CyD, owing to an electrostatic interaction of its carboxylate anion with positive charge of basic drugs. Thus, GUG-beta-CyD may be useful as a safe solubilizing agent particularly for basic drugs.
Tavornvipas
Sumitra
S
Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
Hirayama
Fumitoshi
F
Arima
Hidetoshi
H
Uekama
Kaneto
K
Ishiguro
Toshihiro
T
Oka
Masahide
M
Hamayasu
Kenichi
K
Hashimoto
Hitoshi
H
D000818:Animals; D018938:Caco-2 Cells / Q000187:drug effects / Q000502:physiology; D003505:Cyclodextrins / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D009844:Oligosaccharides / Q000737:chemistry* / Q000494:pharmacology*; D011817:Rabbits; D012995:Solubility
D003505:Cyclodextrins; D009844:Oligosaccharides; C438085:cyclomaltoheptaosyl-(6-1)-glucopyranosyl-(4-1)-glucopyranosiduronic acid