Development of Liposomes as an Efficient Carrier System: New Methodology for Cell Targeting and Intracellular Delivery of Drugs and DNA

  • D. Papahadjopoulos
  • T. Heath
  • F. Martin
  • R. Fraley
  • R. Straubinger
Part of the NATO Advanced Study Institutes Series book series (NSSA, volume 47)


Liposomes are a valuable carrier system for enhancing the pharmacological activity of drugs and the functional incorporation of macromolecules into cells. During the last few years, we have concentrated on developing new liposome methodology designed to optimize their properties as a carrier system. We will describe some of these procedures related to the following specific topics: (1) efficiency of encapsulation: the reverse phase evaporation method produces large unilamellar vesicles (0.2–0.4 μdiameter) encapsulating approximately 50% of the initial aqueous phase. This procedure is particularly valuable for the encapsulation of large macromolecules such as RNA and DNA which can be entrapped with very high efficiency and no appreciable degradation. (2) control of vesicle size: extrusion of liposomes through nucleopore membranes produces vesicles which conform to the membrane pore diameter without loss of material. This allows the preparation of reasonably homogeneous populations of unilamellar vesicles in the range of 0.1–0.2 μ in diameter. (3) control of liposome permeability: minimizing permeability by increasing the cholesterol content increases dramatically in vivo anti-tumour effects. This has been tested with Ara-C containing vesicles against L1210 leukemia in mice. (4) intracellular delivery of macromolecules: the infectivity of liposome-encapsulated SV40 DNA is enhanced up to 1000-fold over free DNA and is dependent on the vesicle lipid compositions and the incubation conditions. The highest infectivity is achieved with vesicles composed of phosphatidylserine and cholesterol (1:1 mole ratio) in the presence of chloroquine, and in conjunction with a short post-incubation treatment with high concentrations of glycerol. Under these conditions, the infectivity of SV40 DNA (3 x 105 pfu/ g DNA) is comparable or greater than can be obtained using the Ca3(PO4)2techniques for DNA delivery. (5) targeting to specific cells: the covalent attachment of cell specific F(ab’)2 and Fab’ fragments of IgG to the liposome surface induces nearly quantitative uptake of liposomes by target cells. These new procedures increase by 100-fold the uptake of liposomes and their contents by the target cells. Current studies involve monoclonal antibodies against a variety of human and murine antigenic determinants.


Lipid Vesicle Intracellular Delivery Phospholipid Vesicle Liposome Preparation Small Unilamellar Vesicle 
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Copyright information

© Plenum Press, New York 1982

Authors and Affiliations

  • D. Papahadjopoulos
    • 1
  • T. Heath
    • 2
  • F. Martin
    • 2
  • R. Fraley
    • 3
  • R. Straubinger
    • 2
  1. 1.Department of PharmacologyUniversity of CaliforniaSan FranciscoUSA
  2. 2.Cancer Research InstituteUniversity of CaliforniaSan FranciscoUSA
  3. 3.Monsanto CompanySt. LouisUSA

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