Complexation with β-cyclodextrin confers oral activity on the flavonoid dioclein

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Dioclein is a flavonoid reported to have many beneficial effects on the cardiovascular system such as vasorelaxant, hypotensive, antioxidant and antiarrythmogenic activities. However, use as pharmaceuticals is limited due to the lack of oral activity and low water solubility. In this work, intending to improve its oral activity, we performed a 1:1 inclusion complex (IC) between dioclein and β-cyclodextrin (β-CD). The IC was characterized by nuclear magnetic resonance and infrared spectroscopy and its vasodilator and hypotensive effects were evaluated in mice. The inclusion of dioclein in β-CD increased the water solubility 44% compared to free dioclein. The IC (2.5 mg kg−1) produced a higher and long lasting change in systolic blood pressure (SBP) after intraperitoneal administration compared to free dioclein. When given orally, free dioclein (10 mg kg−1) showed no hypotensive effect while the IC induced a pronounced decrease in SBP. The in vitro vasodilator effect of dioclein was unchanged by its inclusion in β-CD showing that the IC does not change the interaction between dioclein and its cellular targets. In conclusion, our results show that the new complex prepared by inclusion of dioclein in β-CD improves the hypotensive effect of the flavonoid by increasing its bioavailability and enables dioclein to be effective after oral administration. The mechanism underling the increase in bioavailability is probably a consequence of a protective effect of β-CD against in vivo biodegradation by enzymes and possibly increased water solubility.

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