Investigation of inclusion complexation of paclitaxel by cyclohenicosakis-(1 -> 2)-(beta-D-glucopyranosyl), by cyclic-(1 -> 2)-beta-D-glucans (cyclosophoraoses), and by cyclomaltoheptaoses (beta-cyclodextrins)

Inclusion complexation of the poorly soluble drug, paclitaxel, was investig ated with various host cyclooligosaccharides such as a family of isolated n eutral cyclohenicosakis-(1 --> 2)-(beta -D-glucopyranosyl) (cyclic-(1 --> 2 )-beta -D-glucans, cyclosophoraoses), dimethyl cyclomaltoheptaose (cyclodex trins, DM-beta -CD) and hydroxypropyl cyclomaltoheptaose (cyclodextrins, HP -beta -CD). Quantitative analysis with high-performance liquid chromatograp hy (HPLC) indicated that all three cyclic oligosaccharides could increase t he solubility of paclitaxel, where DM-beta -CD gave the best results and a family of cyclosophoraoses and HP-beta -CD, both gave similar results. Comp lexation of host molecules with paclitaxel was studied by NMR and fluoresce nce spectroscopic analyses. NMR spectroscopic analysis showed that the arom atic regions of paclitaxel experienced noticeable changes of the chemical s hifts or peak shapes upon interaction with host molecules. The relatively b ulky cyclosophoraoses allowed favorable accessibility to either the B-ring or A-ring of paclitaxel, while DM-beta -CD and HP-beta -CD allowed accessib ility to all the aromatic rings including the C ring. The interaction of DM -beta -CD with paclitaxel greatly increased the fluorescence intensity comp ared with other host molecules, suggesting the more effective partitioning of a moderate fluorophore into a hydrophobic cluster adjacent to the C-ring of paclitaxel. (C) 2001 Elsevier Science Ltd. All rights reserved.