Self-assembled micellar formulation of chafuroside A with improved anti-inflammatory effects in experimental asthma/COPD-model rats.

Chafuroside A (CFA), a poorly water-soluble flavone C-glycoside, was firstly isolated from oolong tea, and it acts as a potent anti-inflammatory agent. The present study was undertaken to develop a water-soluble formulation of CFA using a self-assembled micellar (SAM) system, with the aim of improved dissolution behavior and potent anti-inflammatory effects. The SAM formulation of CFA (CFA/SAM) was characterized in terms of its morphology, particle size distribution, crystallinity, and dissolution behavior. In dissolution testing, the CFA/SAM exhibited marked improvement in dissolution behavior when compared with crystalline CFA, and then, nano-micellar particles were constituted with a mean diameter of 84 nm. The therapeutic potential of the crystalline CFA and CFA/SAM was assessed using an experimental asthma/chronic obstructive pulmonary disease (COPD)-like model. Orally-administered CFA at 0.5mg/kg or higher could attenuate inflammatory symptoms in a dose-dependent manner, as evidenced by decreases of infiltrated granulocytes, including macrophages and neutrophils, and myeloperoxidase, a specific biomarker for neutrophilia. Biomarker profiling demonstrated that the CFA/SAM at 0.1mg CFA/kg was equipotent to CFA at 1.0mg/kg in ameliorating antigen-induced airway inflammation, suggesting the better pharmacological effect of CFA/SAM due to improved dissolution behavior. From these observations, the SAM formulation might be an efficacious approach for enhancing the therapeutic potential of CFA for treatment of inflammatory diseases.