Masahide Oka

6-O-α-(4-O-α-D-glucuronyl)-D-glucosyl-β-cyclodextrin: Solubilizing ability and some cellular effects

Some physicochemical and biopharmaceutical properties of a new branched cyclodextrin, 6-O-α-(4-O-α-d-glucuronyl)-d-glucosyl-β-cyclodextrin (GUG-β-CyD), were investigated. The interaction of GUG-β-CyD with drugs was studied by spectroscopic and solubility methods, and compared with those of parent β-CyD and 6-O-α-maltosyl-β-CyD (G2-β-CyD). The hemolytic activity of GUG-β-CyD on rabbit erythrocytes was lower than those of β-CyD and G2-β-CyD. GUG-β-CyD and G2-β-CyD showed negligible cytotoxicity on Caco-2 cells up to at least 0.1 M. The inclusion ability of GUG-β-CyD to neutral and acidic drugs was comparable to or slightly smaller than those of β-CyD and G2-β-CyD, probably because of a steric hindrance of the branched sugar. On the other hand, GUG-β-CyD showed greater affinity for the basic drugs, compared with β-CyD and G2-β-CyD, owing to an electrostatic interaction of its carboxylate anion with positive charge of basic drugs. Thus, GUG-β-CyD may be useful as a safe solubilizing agent particularly for basic drugs.

Some Pharmaceutical Properties of a New Branched Cyclodextrin, 6-O-α-(4-O- α-D-Glucuronyl)-D-glucosylβ-cyclodextrin

Some physicochemical and biological properties of a new branched cyclodextrin, 6-O-α-(4-O-α-d-glucuronyl)-d-glucosyl-β-cyclodextrin GUG-β-CyD) were investigated. Further, theinteraction of GUG-β-CyD with several drugs was studied by the solubility and spectroscopic methods, and compared with those of parent β-CyD and 6-O-α-maltosyl-β-CyD(2-β-CyD).The hemolytic activity of GUG-β-CyD on rabbit erythrocytes was lower than those of β-CyD and 2-β-CyD. GUG-β-CyD and 2-β-CyD showed negligible cytotoxicity on Caco-2 cells up to at least 0.1 M. The inclusion ability of GUG-β-CyD to neutral and acidic drugs was comparable to or slightly smaller than those of β-CyD and 2-β-CyD, probably because of a steric hindrance of the branched sugar. On the other hand, GUG-β-CyD showed greater affinity for the basic drugs, compared with β-CyD and 2-β-CyD, owing to the electrostatic interaction of its carboxylate anion with positive charge of basic drugs. Thus GUG-β-CyD may be useful as a safe solubilizing agent particularly for basic drugs.

Synthesis of branched cyclomaltooligosaccharide carboxylic acids (cyclodextrin carboxylic acids) by microbial oxidation.

Novel branched cyclomaltooligosaccharide carboxylic acid (cyclodextrin carboxylic acid) derivatives were synthesized by microbial oxidation using Pseudogluconobacter saccharoketogenes to oxidize five types of branched cyclodextrins, including maltosyl beta-cyclodextrin (maltosyl-beta-CyD). For each novel cyclodextrin carboxylic acid derivative synthesized, the hydroxymethyl group of the terminal glucose residue in the branched part of the molecule was regiospecifically oxidized to a carboxyl group to give the corresponding uronic acid. In addition, the physicochemical properties of cyclomaltoheptaosyl-(6-->1)-alpha-D-glucopyranosyl-(4-->1)-alpha-D-glucopyranosiduronic acid (GUG-beta-CyD) (1) and its sodium salt were studied more extensively, as these compounds are most likely to have a practical application.