title: Preparation, characterization and tissue distribution of brucine stealth liposomes with different lipid composition.
abstract: OBJECTIVE
  To improve the therapeutic index of brucine, the novel stealth liposomes (SLS-n), composed of naturally unsaturated and hydrogenated soy phosphatidylcholines, with significant difference of phase transition temperature, were developed to encapsulate brucine.
  
  
  METHODS
  Brucine-loaded stealth liposomes with different lipid compositions were prepared and characterized for their entrapment efficiency (EE), particle size, zeta potential and in vitro drug release profile. Tissue distribution after intravenous administration of different brucine formulations was further compared in tumor-bearing mice.
  
  
  RESULTS
  Compared with the conventional stealth liposomes composed of SPC (SLS-s) or HSPC (SLS-h), EE and zeta potential of SLS-n were increased slightly, and the size was decreased slightly. The results of drug release showed that SLS-n were more stable than SLS-s. After intravenous administration, tumor AUC in SLS-s, SLS-n and SLS-h treated animals were 1.33, 1.72 and 2.59-fold higher than in mice treated with the same dose of free brucine, respectively. Compared with brucine solution, administration of SLS-s and SLS-n could significantly decrease brucine concentration in brain, but administration of SLS-h resulting in significantly increased (2.75-fold) concentration in 10 min.
  
  
  CONCLUSIONS
  Since brucine has severe central nervous system toxicity, our study indicated that SLS-n could considerably improve the therapeutic index of brucine.
authors.affiliation: Nanjing Maternity and Child Health Hospital of Nanjing Medical University, Nanjing, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Bao-Chang
authors.initials: BC
authors.lastname: Cai
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
mesh_terms: D000818:Animals; D019540:Area Under Curve; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D007275:Injections, Intravenous; D008081:Liposomes; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D008297:Male; D051379:Mice; D044367:Phase Transition; D010713:Phosphatidylcholines / Q000737:chemistry*; D013025:Glycine max / Q000737:chemistry; D013331:Strychnine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D008081:Liposomes; D010713:Phosphatidylcholines; C083806:brucine; D013331:Strychnine