Delivery of hydrophilic drug doxorubicin hydrochloride-targeted liver using apoAI as carrier

作者：Yuan Yuan; Wang Weina; Wang Baolong; Zhu Haiyan; Zhang Boheng; Feng Meiqing^*

来源：Journal of Drug Targeting, 2013, 21(4): 367-374.

DOI：10.3109/1061186X.2012.757769

• Apolipoprotein A1
• doxorubicin hydrochloride
• high-density lipoprotein
• hydrophilic drug
• liver target

High-density lipoprotein (HDL) particles can deliver cholesterol from peripheral tissues to the liver through apolipoprotein A1 (Apo A1), which specifically binds to the scavenger receptor class B type 1 (SR-B1) receptor on the surface of hepatocytes. Therefore, ApoA1 can be potentially used to target drugs to the liver. In this study, we successfully loaded doxorubicin hydrochloride (Dox or Dox-HCl), which is a hydrophilic drug used in a wide variety of clinical applications, into the core of reconstituted HDL (rHDL prepared by apoAI and egg phospholipids) to form a doxorubicin-HDL complex (rHDL-Dox). The MTT assays showed that rHDL-Dox particles also had higher cytotoxicity against several cells lines compared to free drug or Dox encapsulated into liposomes. A cellular uptake assay demonstrated that rHDL-Dox had higher absorption in SR-BI receptor positive liver cells. Importantly, in vivo experiments showed that rHDL-Dox can reduce tumor growth more effectively than liposomes. In addition, an in vitro hemolysis assay showed that rHDL-Dox caused only limited hemolysis in the case of high doses. Taken together, our findings indicate that rHDL is a safe and effective drug delivery system for targeting liver.

• 出版日期2013-5
• 单位复旦大学