Effective anti-tumor activity of oxaliplatin encapsulated in transferrin-PEG-liposome

Int J Pharm. 2008 Jan 4;346(1-2):143-50. doi: 10.1016/j.ijpharm.2007.06.010. Epub 2007 Jun 16.


Oxaliplatin (trans-L-diaminocyclohexane oxalatoplatinum, L-OHP) is a novel cisplatin derivative that can improve the side effects of cisplatin such as toxicity to the kidneys and peripheral nerve system. However, L-OHP is effective only when combined with 5-Fluorouracil (5-FU) and Leucovorin. The relatively low anti-tumor index of L-OHP alone is because low levels accumulate in tumor tissues due to high partitioning to erythrocytes in vivo. A successful outcome of cancer therapy using L-OHP requires the selective delivery of a relatively high concentration of the drug to tumors. The present study examines tumor-selective delivery of L-OHP using liposomes modified with transferrin-conjugated polyethyleneglycol (TF-PEG-liposomes). Delivery using these liposomes significantly reduced L-OHP partitioning to erythrocytes and improved the circulation time of L-OHP in vivo, resulting in enhanced extravasation of liposomes into tumors. The TF-PEG-liposomes maintained a high L-OHP concentration in tumors for over 72 h after intravenous injection, which was longer than that of the liposomes modified with PEG (PEG-liposomes). Intravenously administered L-OHP encapsulated within TF-PEG-liposomes (L-OHP: 5 mg/kg) suppressed tumor growth more effectively than PEG-liposomes, Bare-liposomes and free L-OHP. Although L-OHP is usually combined with 5-FU and Leucovorin, our results suggest that L-OHP encapsulated within TF-PEG-liposomes has potential for cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / blood
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor
  • Erythrocytes / metabolism
  • Kidney / metabolism
  • Liposomes
  • Liver / metabolism
  • Lung / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / metabolism
  • Organoplatinum Compounds / administration & dosage*
  • Organoplatinum Compounds / blood
  • Organoplatinum Compounds / pharmacokinetics
  • Organoplatinum Compounds / therapeutic use
  • Oxaliplatin
  • Polyethylene Glycols* / chemistry
  • Polyethylene Glycols* / pharmacokinetics
  • Polyethylene Glycols* / therapeutic use
  • Spleen / metabolism
  • Tissue Distribution
  • Transferrin* / chemistry
  • Transferrin* / pharmacokinetics
  • Transferrin* / therapeutic use


  • Antineoplastic Agents
  • Liposomes
  • Organoplatinum Compounds
  • Transferrin
  • Oxaliplatin
  • Polyethylene Glycols