The pharmacokinetics and anti-inflammatory effects of chelerythrine solid dispersions in vivo

Abstract

Chelerythrine (CHE) is a quaternary benzo [c] phenanthridine alkaloid which has a wide array of pharmacological properties. The purpose of this study was to prepare CHE solid dispersions (SDs), which was aimed at increasing bioavailability and anti-inflammation of CHE. Firstly, CHE-SDs was prepared with different carriers using solvent evaporation method. Then the dissolution study in vitro showed that the optimal carrier was PVP K30 and the best proportion of CHE and PVP K30 was 1:10. Solid state characterization was evaluated by the approach of differential scanning calorimetry (DSC). DSC analysis indicated the complete transformation of CHE in the SDs from crystalline to amorphous state. Finally, the pharmacokinetic study demonstrated the relative bioavailability of CHE in CHE-SDs was significantly improved in comparison to that of CHE solution. AUC of CHE-SDs was about 2.36-fold higher than that obtained with CHE solution. Peak concentration (Cmax) and elimination half-life (t1/2,β) were both higher for CHE-SDs than that for CHE solution. Conversely, total body clearance (CLs) and apparent volume of distribution (V/f(c)) were lower for CHE-SDs in comparison with the CHE solution. CHE-SDs significantly improved the anti-inflammatory effect of CHE through inhibiting the levels of TNF-α, IL-6 and NO in mice serum. In summary, the bioavailability and anti-inflammation activity of CHE were significantly improved by making into CHE-SDs.