title: Delivery of hydrophilic drug doxorubicin hydrochloride-targeted liver using apoAI as carrier.
abstract: 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.
authors.affiliation: School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.forename: Weina
authors.initials: W
authors.lastname: Wang
authors.forename: Baolong
authors.initials: B
authors.lastname: Wang
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhu
authors.forename: Boheng
authors.initials: B
authors.lastname: Zhang
authors.forename: Meiqing
authors.initials: M
authors.lastname: Feng
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D016632:Apolipoprotein A-I / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002352:Carrier Proteins / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods; D056945:Hep G2 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008075:Lipoproteins, HDL / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude
chemical_list: D000903:Antibiotics, Antineoplastic; D016632:Apolipoprotein A-I; D002352:Carrier Proteins; D004337:Drug Carriers; D008075:Lipoproteins, HDL; D008081:Liposomes; D004317:Doxorubicin