Molecular model and in vitro antioxidant activity of a water-soluble and stable phloretin/hydroxypropyl-β-cyclodextrin inclusion complex

Phloretin, a dihydrochalcone flavonoid, has been associated with a wide range of biological properties such as antioxidation, antitumor, antidiabetes, skin whiting, etc. However, the instability and aqueous insolubility in its native form decreases its bioavailability and make its usage limited in clinical application. In our study, an inclusion complex of phloretin with hydroxypropyl-β-cyclodextrin (HP-β-CD) that featured improved aqueous solubility and stability was prepared using a simple co-evaporation method. The inclusion complex prepared under a condition of 1:1, 50 °C, 2 h and 500 rpm showed a great enhancement of phloretin aqueous solubility of 54.08 ± 0.05 mg/mL, which was 5808 times higher than that of free phloretin in pure water at 25 °C. The results of phase solubility study and the characterization data from SEM, PXRD, FT-IR and NMR suggested that aromatic ring of one phloretin molecule was merged into the cavity of one HP-β-CD from the narrow side. The in vitro test showed that the inclusion complex still remained an approximately DPPH radical-scavenging capacity compared to the free phloretin at the same concentration. And the stability of phloretin was greatly improved after forming inclusion complex with HP-β-CD. Thus, the phloretin/HP-β-CD inclusion complex would be a promising approach in the clinical application of phloretin in the future.