A novel β-cyclodextrin-rhein conjugate for improving the water solubility and bioavailability of rhein.

Rhein is a potential antitumor agent, but the poor water-solubility restricts its clinical applicability. β-cyclodextrin-drug conjugates provide a possibility to improve the water-solubility of rhein and thereby enhance its bioavailability. A novel β-cyclodextrin-rhein conjugate (β-CD-RH) was synthesized by covalently link β-cyclodextrin with rhein through a 1,8-diamino-3,6-dioxaoctane linker. The structure of β-CD-RH was characterized by 1H NMR, FT-IR, Maldi-tof MS etc. The inclusion style of β-CD-RH in water was detected by 2D NMR. The 2D ROESY spectrum provided details of the rhein moiety encapsulated in the β-CD cavity. The water-solubility of β-CD-RH is up to 3.24 μmol/mL β-CD-RH exhibited higher cytotoxicity than rhein and rhein/β-CD mixture against Hela cells. Our work provides a new way for the preparation of novel β-CD-drug conjugate.