title: Novel self-assembled micelles based on palmitoyl-trimethyl-chitosan for efficient delivery of harmine to liver cancer.
abstract: BACKGROUND
  Polymeric micelles is a safe and effective delivery system, which belong to the targeted delivery system (TDS). An anticancer drug, harmine(HM) is a hydrophobic drug with much adverse effects when used for treatment of liver cancer. Chitosan (CS) is a polysaccharide and can be modified to be an amphiphilic polmer which could self-assemble into micelles and be applied for delivery of hydrophobic drugs.
  
  
  OBJECTIVE
  To synthesize three kinds of novel biodegradable polymers, designated as palmitoyl-trimethyl-CS (TPCS)1, TPCS2 and Lac-TPCS2, and investigate their efficiency and mechanism of delivery HM to liver tumors in vitro and in viro.
  
  
  RESULTS
  The self-assembled micelles presented satisfactory particle size (∼ 200 nm) and drug release characteristics in vitro. It's proved that Lac-TPCS2/HM may enter HepG2 cell through endocytosis. Antitumor experiments in vivo revealed that Lac-TPCS2/HM could significantly inhibit tumor growth and extend the lifetime of mice bearing H22 tumors after intravenous administration. Subsequently in vivo near-infrared fluorescence imaging results demonstrated a satisfactory liver tumor-targeting effect of Lac-TPCS2/HM.
  
  
  CONCLUSIONS
  Three novel polymers hold great potential in the development of nanomedicine for treatment of liver tumors, in particular Lac-TPCS2 exhibits the greatest antitumor potential through active target effect.
authors.affiliation: Soochow University, College of Pharmaceutical Sciences, Department of Pharmaceutics , Suzhou 215123, Jiang Su Province , People's Republic of China +86 0512 65882087 ; +86 0512 65882087 ; zhangxuenong@163.com.
authors.forename: Yong-Yan
authors.initials: YY
authors.lastname: Bei
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Yuan
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Zhou
authors.forename: Wei-Liang
authors.initials: WL
authors.lastname: Chen
authors.forename: Peng
authors.initials: P
authors.lastname: Xia
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Ben-Gang
authors.initials: BG
authors.lastname: You
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Hu
authors.forename: Qiao-Ling
authors.initials: QL
authors.lastname: Zhu
authors.forename: Chun-Ge
authors.initials: CG
authors.lastname: Zhang
authors.forename: Xue-Nong
authors.initials: XN
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D048271:Chitosan / Q000737:chemistry*; D016503:Drug Delivery Systems; D005260:Female; D006247:Harmine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D056945:Hep G2 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D019308:Palmitic Acid / Q000737:chemistry*; D010316:Particle Size
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D008996:Monoamine Oxidase Inhibitors; D019308:Palmitic Acid; D006247:Harmine; D048271:Chitosan
keywords: chitosan derivates; harmine; self-assembled micelles; targeting efficiency; uptake mechanism