title: Pharmacokinetics and tissue distribution of dual-targeting daunorubicin liposomes in mice.
abstract: BACKGROUND
  To circumvent the problem of transporting anticancer drugs across the blood-brain barrier (BBB) to target brain tumors, we have previously developed dual-targeting daunorubicin liposomes modified with 4-aminophenyl-α-D-manno-pyranoside and transferrin molecules. The objective of the present study was to evaluate the pharmacokinetics and distribution of daunorubicin after intravenous administration of dual-targeting daunorubicin liposomes.
  
  
  METHODS
  We evaluated pharmacological parameters in normal KunMing mice. Drug concentrations in plasma, heart, spleen, lung, kidney and brain were measured using HPLC-UV.
  
  
  RESULTS
  The plasma drug concentration-time profile of the daunorubicin dual-targeting liposomes decreased more slowly than free daunorubicin in the initial phase and maintained higher drug levels in the terminal phase, resulting in longer blood exposure to daunorubicin liposomes compared with the free drug. Daunorubicin levels were lower in heart tissue and significantly higher in brain tissue after administration of the dual-targeting liposomes compared with the free drug. Daunorubicin was detected at varying levels in the liver, spleen, lung and kidney tissues.
  
  
  CONCLUSIONS
  Our results indicate that dual-targeting daunorubicin liposomes improve the daunorubicin blood circulation time and show an enhanced drug transport potential across the BBB.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, and School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Ying
authors.forename: He
authors.initials: H
authors.lastname: Wen
authors.forename: Hong-Juan
authors.initials: HJ
authors.lastname: Yao
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Tian
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.forename: Rui-Jun
authors.initials: RJ
authors.lastname: Ju
authors.forename: Xiao-Xing
authors.initials: XX
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.forename: Wan-Liang
authors.initials: WL
authors.lastname: Lu
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy; D002851:Chromatography, High Pressure Liquid; D003630:Daunorubicin / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods; D006207:Half-Life; D008081:Liposomes; D008297:Male; D008362:Mannosides / Q000737:chemistry; D008657:Metabolic Clearance Rate; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D015203:Reproducibility of Results; D014018:Tissue Distribution; D014168:Transferrin / Q000737:chemistry
chemical_list: D000814:Aniline Compounds; D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D008362:Mannosides; D014168:Transferrin; C034056:4-aminophenylmannoside; D003630:Daunorubicin