Morin/hydroxypropyl-β-cyclodextrin inclusion complex showed higher in vivo oral bioavailability and inhibition on LX-2 cell growth

Morin, a bioflavonoid, is known for its wide range of pharmacological benefits. However, poor aqueous solubility and oral bioavailability are significant disadvantages of morin. In this study, the morin/hydroxypropyl-β-cyclodextrin inclusion complexes (MCD IC-1 and MCD IC-2) were prepared, and their bioavailability, cell uptake, toxicity were studied. MCD IC-1 and MCD IC-2 showed enhanced aqueous solubility and oral bioavailability than free morin. Free morin showed limited aqueous solubility (0.104 ± 0.37 ng/μl), while MCD IC-1 and MCD IC-2 significantly enhanced solubility to 136.36 ± 0.18 ng/μl and 188.35 ± 0.32 ng/μl respectively. The oral bioavailability of MCD IC-2 was 4.55 times higher than free morin, with a Cmax of 860.95 ng/ml compared to 250.70 ng/ml of free morin, and area under the concentration-time curve from 0 to 24 h (AUC0-24) was 4779.88 ng/ml.h for MCD IC-2 compared to 1050.32 ng/ml.h for free morin. In vitro cell uptake study in LX-2 cells revealed enhanced uptake of MCD IC-2. Also, MCD IC-2 treatment to culture activated LX-2 cells showed dose-dependent cytotoxicity. All these results highlighted that the MCD IC-2 is likely to improve in vivo oral bioavailability and inhibition of LX-2 cell growth. Further cell culture and pre-clinical studies are essential to determine the anti-fibrotic effect of MCD IC-2 against experimental liver fibrosis cells and animal models.