A combinatorial approach to producing sterically stabilized (Stealth) immunoliposomal drugs

FEBS Lett. 1999 Oct 22;460(1):129-33. doi: 10.1016/s0014-5793(99)01320-4.

Abstract

We have developed a method for producing sterically stabilized immunoliposomal drugs (SIL) readily applicable to a 'mix and match' combinatorial approach for the simple manufacture of a variety of ligand-targeted liposomal drugs. Ligands coupled to the terminus of polyethylene glycol (PEG) in micelles formed from PEG-lipid derivatives (mPEG2000-DSPE) could be transferred into preformed, drug-containing liposomes from the micelles in a temperature- and time-dependent manner. Antibody densities up to 100 microg antibody/micromol of phospholipid, and up to 3 mol% of mPEG2000-DSPE, could be simultaneously transferred from the ligand-coupled micelles into the liposomal outer monolayer with negligible drug leakage from liposomes during transfer and good stability in human plasma. Transfer of anti-CD19 into SIL resulted in a three-fold increase in binding of these liposomes to CD19+ human B cell lymphoma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / chemistry*
  • Antibodies / immunology
  • Antigens, CD19 / immunology
  • Antineoplastic Agents / chemistry
  • Centrifugation, Density Gradient
  • Combinatorial Chemistry Techniques
  • Doxorubicin / chemistry
  • Drug Carriers
  • Humans
  • Immunoglobulin G / chemistry
  • Liposomes / chemistry*
  • Liposomes / immunology
  • Lymphoma, B-Cell / immunology
  • Micelles
  • Phosphatidylethanolamines / chemistry
  • Polyethylene Glycols / chemistry
  • Tumor Cells, Cultured

Substances

  • Antibodies
  • Antigens, CD19
  • Antineoplastic Agents
  • Drug Carriers
  • Immunoglobulin G
  • Liposomes
  • Micelles
  • Phosphatidylethanolamines
  • polyethylene glycol-distearoylphosphatidylethanolamine
  • Polyethylene Glycols
  • Doxorubicin