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Int J Nanomedicine. 2018 Dec 28;14:301-315. doi: 10.2147/IJN.S187888. eCollection 2019.

Co-delivery doxorubicin and silybin for anti-hepatoma via enhanced oral hepatic-targeted efficiency.

Author information

1
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, cyzhu@implad.ac.cn.

Abstract

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:

anti-hepatoma; biodistribution in vivo; cholic acid transporter; doxorubicin; hepatic targeting via oral administration; silybin

PMID:
30643408
PMCID:
PMC6314320
DOI:
10.2147/IJN.S187888
[Indexed for MEDLINE]
Free PMC Article

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