Enhanced doxorubicin delivery to the brain administered through glutathione PEGylated liposomal doxorubicin (2B3-101) as compared with generic Caelyx,(®)/Doxil(®)--a cerebral open flow microperfusion pilot study

J Pharm Sci. 2014 Jul;103(7):1945-1948. doi: 10.1002/jps.23994. Epub 2014 May 6.


The neuroprotective blood-brain barrier (BBB) keeps many drug candidates below therapeutic levels in the central nervous system. Glutathione PEGylated liposomal doxorubicin (2B3-101) has been developed to safely enhance the delivery of doxorubicin to brain tumors. However, doxorubicin concentration in extracellular brain fluid cannot yet be reliably measured using conventional techniques. Cerebral open flow microperfusion (cOFM), a recently developed sampling technique, allows monitoring of drug concentrations in the brain independent of molecular weight and lipophilicity. In combination with cOFM sampling, sodium fluorescein (NaF) is used as a marker for BBB integrity. Rats received one intravenous dose of 7 mg/kg of either 2B3-101 or PEGylated liposomal doxorubicin (generic Caelyx(®)). Blood and cOFM sampling was performed for 5 h after dose injection. NaF concentration in the brain was monitored and remained low indicating an intact BBB. The brain-to-blood ratio of doxorubicin was 4.8-fold higher after administration of 2B3-101 as compared with generic Caelyx(®) (p = 0.0016). In conclusion, by using cOFM it was possible to show that 2B3-101 leads to enhanced doxorubicin concentration in the brain without affecting the BBB integrity.

Keywords: 2B3-101; CNS; Caelyx®; Doxil®; blood brain barrier; cancer; cerebral open flow microperfusion; doxorubicin; drug targeting; liposomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Blood-Brain Barrier / metabolism*
  • Cerebral Cortex / metabolism*
  • Dose-Response Relationship, Drug
  • Doxorubicin / administration & dosage
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / blood
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacokinetics
  • Drug Delivery Systems*
  • Drug Monitoring / methods
  • Fluorescein / pharmacokinetics
  • Glutathione / administration & dosage
  • Glutathione / analogs & derivatives*
  • Glutathione / blood
  • Glutathione / pharmacokinetics
  • Injections, Intravenous
  • Male
  • Microdialysis / methods*
  • Perfusion
  • Permeability
  • Pilot Projects
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / pharmacokinetics
  • Rats, Sprague-Dawley
  • Tissue Distribution


  • glutathione pegylated liposomal doxorubicin
  • liposomal doxorubicin
  • Polyethylene Glycols
  • Doxorubicin
  • Glutathione
  • Fluorescein