ABSTRACT
Although laboratories have tried to synthesize new local anesthetics, currently available local anesthetics rarely provide prolonged regional blockade. New models of sustained-release preparations of local anesthetics with liposomes and microspheres have been studied to prolong the duration of the effects of the local anesthetics. In the present study, we examined whether a complex of a branched cyclodextrin (CD), 6-O-alpha-D-maltosyl-beta-cyclodextrin (G2-beta-CD) and lidocaine could prolong local nerve block when compared with plain lidocaine. The sciatic nerve in male Sprague-Dawley rats was blocked with plain lidocaine (n = 10), the complex of G2-beta-CD + lidocaine (n = 10), or plain G2-beta-CD (n = 4). Sensory block was assessed with a hotplate set at 56 degrees C. The median duration of the block was longer in the complex group than in the plain lidocaine group (110 min; range, 70-150 min vs 55 min; range, 40-80 min; P < 0.05), thus demonstrating that the complex with CyD significantly prolonged the nerve block effect of lidocaine. In conclusion, the present study showed that this encapsulating technique with CyD is useful to expand local anesthetic effect in peripheral nerve blockade.
Subject(s)
Anesthetics, Local , Lidocaine , Nerve Block , Peripheral Nerves/drug effects , beta-Cyclodextrins , Animals , Delayed-Action Preparations , Drug Carriers , Drug Compounding , Male , Pain Measurement/drug effects , Rats , Rats, Sprague-Dawley , beta-Cyclodextrins/chemistryABSTRACT
A synthetic beta-thio-fructofuranoside of mercaptoethanol inhibited not only beta-fructofuranosidases but also alpha-glucosidases. The compound was hardly hydrolyzed by the glycosidases. The thio-fructoside competitively inhibited beta-fructofuranosidases from Aspergillus niger, Candida sp., and Saccharomyces cerevisiae, but not Arthrobacter beta-fructofuranosidase at all. Sucrase activity of rat intestinal sucrase/isomaltase complex was also suppressed in the presence of the thio-fructoside. The thio-fructoside showed noncompetitive inhibition toward maltase activity of the rat intestinal enzyme complex and Saccharomyces sp. alpha-glucosidase. Inhibition against the Bacillus stearothermophilus alpha-glucosidase, Rhizopus glucoamylase, and porcine kidney trehalase were more slight than that against these two alpha-glucosidases.
Subject(s)
Fructose/analogs & derivatives , Fructose/pharmacology , Glycoside Hydrolase Inhibitors , Sulfides/pharmacology , beta-Fructofuranosidase/antagonists & inhibitors , Animals , Arthrobacter/enzymology , Aspergillus niger/enzymology , Binding, Competitive , Candida/enzymology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/metabolism , Enzyme Inhibitors/pharmacology , Fructose/metabolism , Geobacillus stearothermophilus/enzymology , Glucan 1,4-alpha-Glucosidase/metabolism , Hydrolysis , Intestines/enzymology , Kinetics , Maltose/metabolism , Rats , Rhizopus/enzymology , Saccharomyces cerevisiae/enzymology , Sucrase/metabolism , Sucrose/metabolism , Sulfides/chemistry , Sulfides/metabolism , Swine , Trehalase/metabolismABSTRACT
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.
Subject(s)
Cyclodextrins/chemistry , Cyclodextrins/pharmacology , Oligosaccharides/chemistry , Oligosaccharides/pharmacology , Animals , Caco-2 Cells/drug effects , Caco-2 Cells/physiology , Humans , Rabbits , SolubilityABSTRACT
Mannosylated derivatives of cyclodextrins (CDs), mannosyl-α, ß, and γCD were synthesized from a mixture of mannose and α, ß, and γCD by the reverse action of α-mannosidase from jack bean, respectively. Their structures were analyzed by FAB-MS and 13C-NMR spectroscopies, and they were identified as 6-O-α-d-mannosyl-α, ß, and γCD. The optimum conditions for the production of 6-O-α-d-mannosyl-αCD by α-mannosidase were examined. Optimum pH and temperature were pH 4.5 and 60°C, respectively. Yield of mannosyl-αCD increased with increasing mannose concentration and reached more than 35% (mol/mol) at the concentration of 2 m mannose and 0.4 m αCD.
