Enhanced Distribution and Anti-Tumor Activity of Ergosta-4,6,8(14),22-Tetraen-3-One by Polyethylene Glycol Liposomalization

Abstract

Ergosta-4,6,8(14),22-tetraen-3-one (ergone) was isolated from P. umbellatus, which has been demonstrated to possess a variety of pharmacological activities in vivo and in vitro. The purpose of this study was to evaluate the potent ergone formulations for cancer chemotherapy, the liposomal formulations were less toxic and provide longer systemic circulation time were selected as candidates of nanocarriers for ergone. The effect of modification polyethylene glycol (PEG) on the pharmacokinetics of liposome showed that the retaining time of ergone in blood circulation was prolonged by modified PEG. Moreover, the results of pharmacokinetic analysis showed that of PEG liposome was about 2.8 times higher than that of free PEG liposome after intravenous injection into normal rats due to the lower distribution into the reticuloendothelial system tissues. Since PEG liposome was able to stably encapsulate ergone in blood, area under plasma concentration-time curve of ergone was also extensively enhanced after intravenous dosing of ergone-PEG liposome into normal rats. In the in vivo studies utilizing solid tumor-bearing mice, it was confirmed that ergone-PEG liposome delivered remarkably larger amount of ergone to tumor tissue and provided more significant anti-tumor activity than free ergone. In conclusion, PEG liposome was an effective delivery formulation to achieve increased ergone release in tumor and therapeutic efficacy.