title: In-vivo pharmacokinetics, tissue distribution and anti-tumour effect of hydroxycamptothecin delivered in oil-in-water submicron emulsions.
abstract: OBJECTIVE
  The aim of this study was to investigate the pharmacokinetics, tissue distribution and anti-tumour effect of hydroxycamptothecin submicron emulsions (HCPT-SEs).
  
  
  METHODS
  HCPT-SEs or HCPT injection (HCPT-I) was administered intravenously into the tail vein of rats or S180 tumour-bearing mice.
  
  
  RESULTS
  HCPT-SEs increased the plasma concentration of HCPT compared with HCPT-I at all time points. The AUC(0-∞) , elimination half-life and mean residence time of anionic submicron emulsions containing HCPT (HCPT-ASEs) and cationic submicron emulsions containing HCPT (HCPT-CSEs) were significantly greater than those of HCPT-I (P  <0.01). Especially, a prolonged elimination half-life was found for HCPT-CSEs. HCPT-CSEs and HCPT-ASEs resulted in a 7.9-fold and 3.1-fold increase in AUC(0-6h) of tumour compared with HCPT-I, respectively. The targeting efficiency (T(e) ) of HCPT-ASEs and HCPT-CSEs indicated their selectivity to tumour and the T(e) of HCPT-CSEs was significantly higher than that of HCPT-ASEs (P<0.01). The anti-tumour effect studies showed that HCPT-SEs improved the therapeutic efficiency of HCPT compared with HCPT-I. The percentage of tumour growth suppression rate of mice treated with HCPT-CSEs (2.0 mg HCPT eq./kg) increased 2.1 fold compared with that of HCPT-I.
  
  
  CONCLUSIONS
  Submicron emulsions can alter the pharmacokinetic characteristics and tissue distribution of HCPT, and enhance tumour targeting and anti-tumour activity.
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Yong-Xing
authors.initials: YX
authors.lastname: Zhao
authors.forename: Dan-Xing
authors.initials: DX
authors.lastname: Liu
authors.forename: Wen-Quan
authors.initials: WQ
authors.lastname: Liang
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Ye
mesh_terms: D000818:Animals; D000838:Anions; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D019540:Area Under Curve; D029769:Camptotheca / Q000737:chemistry*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D002412:Cations; D004337:Drug Carriers / Q000493:pharmacokinetics*; D004655:Emulsions / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009369:Neoplasms / Q000188:drug therapy*; D009821:Oils; D008517:Phytotherapy; D010936:Plant Extracts / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014867:Water
chemical_list: D000838:Anions; D000972:Antineoplastic Agents, Phytogenic; D002412:Cations; D004337:Drug Carriers; D004655:Emulsions; D009821:Oils; D010936:Plant Extracts; D014867:Water; D002166:Camptothecin