Pharmacokinetics of differently designed immunoliposome formulations in rats with or without hepatic colon cancer metastases

Pharm Res. 2001 Sep;18(9):1291-8. doi: 10.1023/a:1013085811044.


Purpose: Compare pharmacokinetics of tumor-directed immunoliposomes in healthy and tumor-bearing rats (hepatic colon cancer metastases).

Methods: A tumor cell-specific monoclonal antibody was attached to polyethyleneglycol-stabilized liposomes, either in a random orientation via a lipid anchor (MPB-PEG-liposomes) or uniformly oriented at the distal end of the PEG chains (Hz-PEG-liposomes). Pharmacokinetics and tissue distribution were determined using [3H]cholesteryloleylether or bilayer-anchored 5-fluoro[3H]deoxyuridine-dipalmitate ([3H]FUdR-dP) as a marker.

Results: In healthy animals clearance of PEG-(immuno)liposomes was almost log-linear and only slightly affected by antibody attachment; in tumor-bearing animals all liposomes displayed biphasic clearance. In normal and tumor animals blood elimination increased with increasing antibody density; particularly for the Hz-PEG-liposomes, and was accompanied by increased hepatic uptake, probably due to increased numbers of macrophages induced by tumor growth. The presence of antibodies on the liposomes enhanced tumor accumulation: uptake per gram tumor tissue (2-4% of dose) was similar to that of liver. Remarkably, this applied to tumor-specific and irrelevant antibody. Increased immunoliposome uptake by trypsin-treated Kupffer cells implicated involvement of high-affinity Fc-receptors on activated macrophages.

Conclusions: Tumor growth and immunoliposome characteristics (antibody density and orientation) determine immunoliposome pharmacokinetics. Although with a long-circulating immunoliposome formulation, efficiently retaining the prodrug FUdR-dP, we achieved enhanced uptake by hepatic metastases, this was probably not mediated by specific interaction with the tumor cells, but rather by tumor-associated macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / pharmacokinetics*
  • Antigens, Neoplasm / immunology
  • Antigens, Surface / immunology
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology*
  • Drug Carriers
  • Drug Delivery Systems
  • Immunoglobulin G / immunology
  • Kupffer Cells / metabolism
  • Liposomes / pharmacokinetics*
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / secondary*
  • Rats
  • Rats, Inbred Strains
  • Tissue Distribution
  • Tumor Cells, Cultured


  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Antigens, Surface
  • Drug Carriers
  • Immunoglobulin G
  • Liposomes