Glioma targeting and blood-brain barrier penetration by dual-targeting doxorubincin liposomes

Biomaterials. 2013 Jul;34(22):5628-39. doi: 10.1016/j.biomaterials.2013.03.097. Epub 2013 Apr 26.

Abstract

Effective chemotherapy for glioblastoma requires a carrier that can penetrate the blood-brain barrier (BBB) and subsequently target the glioma cells. Dual-targeting doxorubincin (Dox) liposomes were produced by conjugating liposomes with both folate (F) and transferrin (Tf), which were proven effective in penetrating the BBB and targeting tumors, respectively. The liposome was characterized by particle size, Dox entrapment efficiency, and in vitro release profile. Drug accumulation in cells, P-glycoprotein (P-gp) expression, and drug transport across the BBB in the dual-targeting liposome group were examined by using bEnd3 BBB models. In vivo studies demonstrated that the dual-targeting Dox liposomes could transport across the BBB and mainly distribute in the brain glioma. The anti-tumor effect of the dual-targeting liposome was also demonstrated by the increased survival time, decreased tumor volume, and results of both hematoxylin-eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling analysis. The dual-targeting Dox liposome could improve the therapeutic efficacy of brain glioma and were less toxic than the Dox solution, showing a dual-targeting effect. These results indicate that this dual-targeting liposome can be used as a potential carrier for glioma chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Biological Transport / drug effects
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / pathology*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Doxorubicin / administration & dosage*
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use*
  • Doxorubicin / toxicity
  • Drug Delivery Systems*
  • Folic Acid / metabolism
  • Glioma / drug therapy*
  • Glioma / pathology
  • Humans
  • Liposomes
  • Male
  • Mice
  • Permeability / drug effects
  • Phosphatidylethanolamines / chemical synthesis
  • Phosphatidylethanolamines / chemistry
  • Polyethylene Glycols / chemical synthesis
  • Polyethylene Glycols / chemistry
  • Rats
  • Rats, Wistar
  • Survival Analysis
  • Transferrin / metabolism

Substances

  • Antineoplastic Agents
  • Liposomes
  • Phosphatidylethanolamines
  • Transferrin
  • 1,2-distearoylphosphatidylethanolamine
  • Polyethylene Glycols
  • Doxorubicin
  • Folic Acid