Abstract
Examination was made of the effects of 2-(trimethylsilyl)ethyl 4-Ο-methyl-β-D-glucopyranosyluronic acid-(1→6)-β-D-galactopyranoside (A), 2-(trimethylsilyl)ethyl 4-Ο-methyl-β-D-glucopyranosyluronic acid-(1→6)-β-D-galactopyranosyl-(1→6)-β-D-galactopyranoside (B) and N, N',N''-tri-{5-[4-Ο-methyl-β-D-glucopyranosyluronic acid-(1→6)-β-D-galactopyranosyloxy]pentylcarbonylaminoethyl}-1,3,5-benzenetriamide (C), each possessing the glucuronic acid residue, on drug degradation. Oligosaccharide mixed micelles containing the nonionic surfactant, heptaethyleneglycol dodecylether (HED), were studied so as to assess oligosaccharides A∼C for drug stabilization potential. The nonionic surfactant was required since oligosaccharides A∼C do not form micelles in single systems. Base-catalyzed dehydration and then isomerization of prostaglandin E2 (PGE2), PGE2→PGA2→PGB2, were conducted as model experiments. The rate of the degradation of PGE2 with base was determined based on concentrations of PGA2 and PGB2 using high-performance liquid chromatography. Mixed oligosaccharide-HED micelles inhibited the dehydration and isomerization of PGE2, possibly owing to suppression of the approach of OH- as catalysis toward PGE2 in mixed oligosaccharide-HED micelles by electrostatic repulsion between negatively charged micellar surfaces and OH-. The clusterized molecular structure of oligosaccharide C was the reason for the inhibition of both these processes. Oligosaccharide C may possibly be situated on the micellar surface and this would lead to greater steric shielding and the above electrostatic repulsion compared to A or B.
