Enhanced nematocidal activity of a novel Artemisia extract formulated as a microemulsion

Abstract

Some species of Artemisia have traditionally been used as anthelmintics. The presence of toxic components in the extracts of these plants, such as α- and β-thujones, and their poor aqueous solubility constitutes important limitations for their clinical applications. Recently, some thujones-free populations of A. absinthium have been cultivated in Zaragoza (Spain). The main aim of the present study was to design novel microemulsion (ME) formulations of thujones-free A. absinthium steam distilled extract (AAE) to improve its solubility and, subsequently, to enhance its oral bioavailability and nematocidal activity. A D-optimal mixture design was developed to optimize the ME system, based on droplet size distribution. The optimized formulation was analyzed for its conductivity and behavior in a gastric media and its nematocidal efficacy was evaluated in an ex vivo murine model for Trichinella spiralis larvae L1. The optimized ME was composed of Tween 80: propylene glycol (1.5:1) (66.45% w/w), AAE (29.35% w/w), and distilled water (4.25% w/w). It was seen that although the optimized ME has a W/O structure, it is capable of dispersing in the gastric environment in less than 15 minutes, forming 10 nm-sized droplets. A dilution of this ME, containing 0.05% w/w AAE, was prepared and its efficacy was compared with a 0.05% w/w AAE solution. The optimized ME decreased the intestinal parasites by up to 95.7%, while the solution of the extract showed a reduction of 86.5% (P = 0.0033). The results evidenced that the designed ME system provides a significant improvement of AAE in terms of aqueous solubility and nematocidal effect. It can also act as a promising formulation to improve the oral bioavailability of this hydrophobic extract, in order to design a future alternative to the classical treatments with benzimidazole drugs.