Novel biomineral-binding cyclodextrins for controlled drug delivery in the oral cavity.

A biomineral-binding alendronate-beta-cyclodextrin conjugate (ALN-beta-CD, Fig. 1) was developed as a novel drug delivery system. "Click" chemistry was used in conjugation of alendronate (ALN) to beta-cyclodextrin (beta-CD). The delivery system shows very strong binding to hydroxyapatite (HA, main component of tooth enamel). Its ability in forming molecular inclusion complex with dexamethsone (Dex, model drug) was investigated independently with phase solubility experiments, isothermal titration calorimetry (ITC), Job plot and (1)H NMR. The stoichiometry of ALN-beta-CD/Dex molecular complex was determined as 1:1, and the binding constant of the complex obtained from ITC study is 3.8 x 10(3) M(-1), which is similar to the binding constant of beta-CD/Dex. In vitro data indicate that the ALN-beta-CD/Dex complex bound to HA could gradually release Dex upon repeated extraction with phosphate buffer saline (PBS). This novel drug delivery system may have great potential in improving treatment of diseases in the oral cavity.