Unveiling the complexation mechanism of phloretin with Sulfobutylether-fl-cyclodextrin (Captisol®) and its impact on anticancer activity

The incorporation of phloretin (PHL), a dihydrochalcone flavonoid, in functional foods is usually hampered by its low aqueous solubility. In this regard, we investigated the impact of complexation of PHL with sulfobutyletherfl-cyclodextrin (SBE-fl-CD, Captisol (R)) to overcome its limitation. The phase solubility studies of PHL with different fl-CDs derivatives represents AL-type of curve where, SBE-fl-CD demonstrated highest apparent stability constant (Ks: 15,856 M-1) indicating its strong affinity to form host-guest assembly. Solid-state characterizations (including SEM, FT-IR, PXRD, DSC, TGA) provided direct evidences of inclusion complex (IC) formation. The detailed molecular interaction between the host-guest assembly was performed using 1H NMR and 2D-NOESY revealed that protons of aromatic phenyl ring of PHL (guest) molecule exhibit direct correlation with the protons lying in the inner cavity of SBE-fl-CD (host). Furthermore, the anticancer potential of PHL/SBE-fl-CD-IC was examined using cytotoxicity studies, caspase 3/7 activation assay, reactive oxygen species (ROS) generation and disturbance in mitochondrial membrane potential (MMP) in lung carcinoma cell line (A549) and human pancreatic cancer cell line (MiaPaCa-2). The in-vitro cytotoxicity assay on both cell lines demonstrated higher antiproliferative activity of IC as compared to free PHL in concentration dependent manner. In addition, it was found that PHL/SBE-fl-CD-IC induces apoptosis via activation of caspase 3/7, reactive oxygen species generation and inducing depolarization of mitochondrial membrane potential in both the cell lines (MiaPaCa-2 and A549). Overall, the study provides a promising approach to enhance the solubility and bioactivity of PHL utilizing SBEfl-CD inclusion complexation.

Automated summary

This study investigated the complexation of phloretin with sulfobutyletherfl-cyclodextrin to enhance its solubility and examined the anticancer potential of the complex. The results showed that the complex had higher antiproliferative activity against lung carcinoma and pancreatic cancer cells compared to free phloretin.