Preparation of a nanoscale dihydromyricetin-phospholipid complex to improve the bioavailability: in vitro and in vivo evaluations

Abstract

Dihydromyricetin (DMY), a flavanonol compound found as the most abundant and bioactive constituent in Ampelopsis grossedentata (Hand-Mazz) W.T. Wang, possesses numerous pharmacological activities, such as antioxidant, anti-inflammation, anticancer, anti-microbial, hypoglycemic and hypolipidemic effects, and so on. Recently, DMY shows a promising potential to develop as an agent for the prevention and treatment of Type 2 diabetes mellitus (T2DM). However, the low oral bioavailability of DMY was one of the special concerns to be resolved for its clinical applications. In this study, DMY phospholipid complex (DMY-HSPC COM) was prepared by the solvent evaporation technique and optimized with DMY combination ratio. Scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier transform infrared spectrophotometry (FT-IR) were carried to characterize the formation of DMY-HSPC COM. The particle size, zeta potential, drug loading and solubility of DMY-HSPC COM were further investigated. The phospholipid complex technology could significantly improve the solubility of DMY. Pharmacokinetic study results of DMY-HSPC COM in healthy SD rats and T2DM rats demonstrated that the oral bioavailability was significantly increased when compared with pure DMY as well, which could be attributed to the improvement of the aqueous solubility of the complex, absorption promotion and a probable decrease in intestinal and hepatic metabolism. In addition, when compared with healthy SD rats, pharmacokinetic parameters of pure DMY and DMY-HSPC COM showed significant difference in T2DM rats. Thus, phospholipid complex technology holds a promising potential for increasing the oral bioavailability of DMY.