Co-delivery doxorubicin and silybin for anti-hepatoma via enhanced oral hepatic-targeted efficiency.
Int J Nanomedicine. 2019 ;14:301-315. Epub 2018 Dec 28. PMID: 30643408
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.