International Journal of Nanomedicine (Dec 2018)
Co-delivery doxorubicin and silybin for anti-hepatoma via enhanced oral hepatic-targeted efficiency
Abstract
Ying Li, Dandan Yang, Yian Wang, Zhan Li, Chunyan Zhu Drug Delivery Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, People’s Republic of China Background: To establish the combination of doxorubicin (DOX) and silybin (SLB) in oral hepatic-targeting liposomes with the goal of reducing cardiotoxic side effects and improve oral hepatoma treatment. Methods: Distearoylphosphatidylethanolamine–polyethylene glycol–cholic acid-modified liposomes (CA-LP) were used to encapsulate DOX and SLB (CA-LP–DOX/SLB), and the hepatic targeting, efficacy against hepatoma and cardioprotective effects were evaluated by cell toxicity, scratch and apoptosis in vitro studies, and pharmacokinetics and pharmacodynamics in vivo studies. Results: In vitro cell studies showed that CA-LP–DOX/SLB inhibited HepG2 cell proliferation and HCC97H cell migration, and protected H9c2 cells. In vivo pharmacokinetics demonstrated that the CA-LP–DOX/SLB-treated group showed higher liver accumulation and lower heart accumulation of DOX relative to those in the CA-LP–DOX and LP–DOX-treated groups. In vivo pharmacodynamic studies showed that the CA-LP–DOX/SLB-treated group not only efficiently inhibited growth but also induced significantly less tissue damage than that observed in the CA-LP–DOX-treated group. Conclusion: Concurrent administration of DOX and SLB via CA-LP provided a viable strategy to mitigate acute DOX-induced cardiotoxicity. Keywords: doxorubicin, silybin, hepatic targeting via oral administration, cholic acid transporter, anti-hepatoma, biodistribution in vivo
