We found dramatically increased binding between cyclodextrins (CDs) and alpha-mangostin (MGS) when CDs were incorporated into nanoparticles with polymerized epichlorohydrin. In this study, based on the 1:1 association model of MGS/CD, the binding constant was evaluated. Surprisingly, the binding constant was increased by almost 100 times and reached the same level of ligand-receptor interactions as in biological systems.