Three kinds of β-cyclodextrin derivatives conjugated with glucose moieties, which were expected as models for a drug carrier targeting the drug delivery systems, were designed and synthesized from β-cyclodextrin and the natural product, 4-hydroxyphenyl-β-D-glucopyranoside called arbutin. Arbutin was used because it had a phenyl group with a hydroxyl function which could be used to link the glucose moiety to β-cyclodextrin. The evaluations of these conjugates as the drug-carrying molecules were done by investigating the molecular interactions with the carbohydrate-binding Concanavalin A (Con A) lectin and the anticancer agent, doxorubicin (DXR), using an SPR optical biosensor. The association constants of the conjugates with immobilized Con A were 2.0 x 103 ∼ 8.8 x 103 M – 1. The result showed that the Con A bound to the glucose moieties from arbutin in the conjugates with prospective association constants. The inclusion associations of the conjugates with immobilized DXR reached 2.2 x 105 ∼ 1.4 x 108 M – 1. The extremely high inclusion associations for DXR suggested their potential abilities as drug-carrying molecules for carrying DXR. The NMR analyses indicated that the phenyl group of the conjugates greatly served to increase the inclusion associations for DXR. In their DXR inclusion complexes, the formation of the stacking complexes by the π – π interactions between the phenyl groups and the included DXR also enhanced their inclusion abilities for DXR.
Keywords: Cyclodextrin, drug delivery system, drug carrier, stacking effect, arbutin, doxorubicin