Investigation of inclusion complexation of paclitaxel by cyclohenicosakis-(1→2)-(β- d-glucopyranosyl), by cyclic-(1→2)-β- d-glucans (cyclosophoraoses), and by cyclomaltoheptaoses (β-cyclodextrins)

Inclusion complexation of the poorly soluble drug, paclitaxel, was investigated with various host cyclooligosaccharides such as a family of isolated neutral cyclohenicosakis-(1→2)-(β- d-glucopyranosyl) (cyclic-(1→2)-β- d-glucans, cyclosophoraoses), dimethyl cyclomaltoheptaose (cyclodextrins, DM-β-CD) and hydroxypropyl cyclomaltoheptaose (cyclodextrins, HP-β-CD). Quantitative analysis with high-performance liquid chromatography (HPLC) indicated that all three cyclic oligosaccharides could increase the solubility of paclitaxel, where DM-β-CD gave the best results and a family of cyclosophoraoses and HP-β-CD, both gave similar results. Complexation of host molecules with paclitaxel was studied by NMR and fluorescence spectroscopic analyses. NMR spectroscopic analysis showed that the aromatic regions of paclitaxel experienced noticeable changes of the chemical shifts or peak shapes upon interaction with host molecules. The relatively bulky cyclosophoraoses allowed favorable accessibility to either the B-ring or A-ring of paclitaxel, while DM-β-CD and HP-β-CD allowed accessibility to all the aromatic rings including the C ring. The interaction of DM-β-CD with paclitaxel greatly increased the fluorescence intensity compared with other host molecules, suggesting the more effective partitioning of a moderate fluorophore into a hydrophobic cluster adjacent to the C-ring of paclitaxel. Inclusion complexation of (a) paclitaxel by (d) cyclohenicosakis-[(1→2)-β- d-glucopyranosyl], cyclic (1→2)-β- d-glucans (cyclosophoraoses) shows the different molecular mechanism compared with thst of derivatized cyclomaltoheptaoses (β-cyclodextrins) (b or c).