Tumor cell targeting of liposome-entrapped drugs with phospholipid-anchored folic acid-PEG conjugates

Adv Drug Deliv Rev. 2004 Apr 29;56(8):1177-92. doi: 10.1016/j.addr.2004.01.011.

Abstract

Targeting of liposomes with phospholipid-anchored folate conjugates is an attractive approach to deliver chemotherapeutic agents to folate receptor (FR) expressing tumors. The use of polyethylene glycol (PEG)-coated liposomes with folate attached to the outer end of a small fraction of phospholipid-anchored PEG molecules appears to be the most appropriate way to combine long-circulating properties critical for liposome deposition in tumors and binding of liposomes to FR on tumor cells. Although a number of important formulation parameters remain to be optimized, there are indications, at least in one ascitic tumor model, that folate targeting shifts intra-tumor distribution of liposomes to the cellular compartment. In vitro, folate targeting enhances the cytotoxicity of liposomal drugs against FR-expressing tumor cells. In vivo, the therapeutic data are still fragmentary and appear to be formulation- and tumor model-dependent. Further studies are required to determine whether folate targeting can confer a clear advantage in efficacy and/or toxicity to liposomal drugs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Cell Line, Tumor
  • Drug Delivery Systems / methods*
  • Folic Acid / administration & dosage*
  • Humans
  • Liposomes
  • Phospholipids / administration & dosage*
  • Polyethylene Glycols / administration & dosage*

Substances

  • Antineoplastic Agents
  • Liposomes
  • Phospholipids
  • Polyethylene Glycols
  • Folic Acid