Application of Ganoderma lucidum extract for constructing an oral docetaxel delivery system

Abstract

Docetaxel is one of the most valuable chemotherapeutic drugs, but it has extremely low oral bioavailability. In this study, an oral docetaxel delivery system was constructed based on the extract of Ganoderma lucidum, a well-known medicinal mushroom. First, a G. lucidum extract-docetaxel complex was prepared by stirring and freeze-drying. Results demonstrated that, compared to the docetaxel group, the exposure levels of docetaxel in the complex group were significantly increased in the mouse portal vein (Cmax, 599.7 vs. 58.5 ng/mL; AUC0–12 h, 631.2 vs. 185.9 ng·h/mL), systemic circulation (Cmax, 310.4 vs. 34.9 ng/mL; AUC0–12 h, 467.6 vs. 124.7 ng·h/mL), liver (Cmax, 431.2 vs. 58.4 ng/g liver; AUC0–12 h, 2007.3 vs. 473.0 ng·h/g liver), and lungs (Cmax, 1711.3 vs. 362.7 ng/g lung; AUC0–12 h, 5188.5 vs. 1329.5 ng·h/g lung). Moreover, in the complex group, except for metabolic stability (p > 0.05), transportation from the mucosal side of gut sacs to the serosal side (p < 0.01), solubility (52.6 vs. 4.2 μg/mL), and release of docetaxel in water were significantly improved (15 min, 5.5% vs. 2.3%; 8 h, 35.0% vs. 15.1%). Furthermore, scanning electron microscope (SEM), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD) analysis demonstrated the amorphous existing form of docetaxel. In conclusion, the pharmacokinetics of oral docetaxel in mice was improved by the G. lucidum extract-docetaxel complex, which changed the existing form of docetaxel from crystalline to amorphous. This study provides a simple solution to docetaxel’s low oral bioavailability.