Studies On Evodiamine Phospholipid Complex

The phytosome technology, first investigated for cosmetic applications, has been proven to be a potential drug delivery system for the clinical applicability of active phyto-constituent with poor bioavailability. The solubility and bioavailability could be greatly enhanced by phytosome technology.Evodiamine (EVO), a quinoline alkaloid, is extracted from the fruit of a Chinese herb (Evodia rutaecarpa, namely Wu-Chu-Yu in Chinese) and has been shown to possess various pharmacological effects, such as antitumor, anti-inflammatory, antinociceptive, anti-obesity, thermoregulatory. Despite the promising biological effects of EVO, clinical translation of these results was hampered by its extremely poor oral bioavailability.The aim of this research was to formulate evodiamine–phospholipid complex (EVO-PLC) in attempt to increase the bioavailability of EVO.A central composite design approach was employed for process optimization. The physicochemical properties of EVO-PLC were investigated by means of differential scanning calorimetry (DSC), ultraviolet (UV) spectroscopy and fourier transformed infrared (FT-IR) spectroscopy . After oral administration of EVO-PLC,the concentrations of EVO at different time in rats were determined by HPLC and the pharmacokinetic parameters were computed by software DAS 2.1.1. Multiple linear regression analysis for process optimization revealed that the acceptable EVO–PLC was obtained wherein the optimal values of X1, X2 and X3 were 2, 0.5 and 2.5 mg·ml^-1, respectively. The average particle size and zeta potential of EVO-PLC obtained by the optimized formulation were 246.1 nm and -26.94 mV, respectively. The EVO and phospholipids in the EVO–PLC were combined by non-covalent bond, not forming a new compound. The solubility of EVO-PLC in water was effectively enhanced. Mean plasma concentration-time curve of EVO after oral administration of EVO-PLC and EVO in rats was both in accordance with open two-compartment mode. Pharmacokinetic parameters of EVO-PLC and EVO material in rats were Tmax 8 h and 4 h; Cmax 599.66 and 352.01μg·L^-1; AUC0–∞3878.24 and 1772.36μg·h·L^-1, respectively. The bioavailability of EVO in rats was increased remarkably after oral administration of EVO-PLC, compared with that of EVO. This was mainly due to an improvement of the solubility of EVO-PLC.