Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse-phase evaporation.

Large unilamellar and oligolamellar vesicles are formed when an aqueous buffer is introduced into a mixture of phospholipid and organic solvent and the organic solvent is subsequently removed by evaporation under reduced pressure. These vesicles can be made from various lipids or mixtures of lipids and have aqueous volume to lipid ratios that are 30 times higher than sonicated preparations and 4 times higher than multilamellar vesicles. Most importantly, a substantial fraction of the aqueous phase (up to 62% at low salt concentrations) is entrapped within the vesicles, encapsulating even large macromolecular assemblies with high efficiency. Thus, this relatively simple technique has unique advantages for encapsulating valuable water-soluble materials such as drugs, proteins, nucleic acids, and other biochemical reagents. The preparation and properties of the vesicles are described in detail.

[1]  S. T. Sun,et al.  Dynamic light scattering study of calcium-induced fusion in phospholipid vesicles. , 1977, Biochimica et biophysica acta.

[2]  T. Ray,et al.  A modified method for the isolation of the plasma membrane from rat liver. , 1970, Biochimica et biophysica acta.

[3]  A. Bangham,et al.  Diffusion of univalent ions across the lamellae of swollen phospholipids. , 1965, Journal of molecular biology.

[4]  D. Papahadjopoulos,et al.  Phospholipid model membranes. II. Permeability properties of hydrated liquid crystals. , 1967, Biochimica et biophysica acta.

[5]  D. Papahadjopoulos,et al.  Biological properties of poliovirus encapsulated in lipid vesicles: antibody resistance and infectivity in virus-resistant cells. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[6]  R. Garry,et al.  Interferon Induction by Poly(I):Poly(C) Enclosed in Phospholipid Particles , 1974, Infection and Immunity.

[7]  T. Yotsuyanagi,et al.  Model transport studies utilizing lecithin spherules. I. Critical evaluations of several physical models in the determination of the permeability coefficient for glucose. , 1972, Biochimica et biophysica acta.

[8]  G. Poste,et al.  Membrane fusion and molecular segregation in phospholipid vesicles. , 1974, Biochimica et biophysica acta.

[9]  K. Jacobson,et al.  Phase transitions in phospholipid vesicles. Fluorescence polarization and permeability measurements concerning the effect of temperature and cholesterol. , 1973, Biochimica et biophysica acta.

[10]  E. Korn,et al.  Single bilayer liposomes prepared without sonication. , 1973, Biochimica et biophysica acta.

[11]  D. Papahadjopoulos Liposomes and their uses in biology and medicine. , 1978, Annals of the New York Academy of Sciences.

[12]  K. Jacobson,et al.  Cochleate lipid cylinders: formation by fusion of unilamellar lipid vesicles. , 1975, Biochimica et biophysica acta.

[13]  F. Greenwood,et al.  THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY. , 1963, The Biochemical journal.

[14]  S. Dray,et al.  Incorporation of high molecular weight RNA into large artificial lipid vesicles. , 1977, Biochemical and biophysical research communications.

[15]  D. Deamer PREPARATION AND PROPERTIES OF ETHER‐INJECTION LIPOSOMES * , 1978, Annals of the New York Academy of Sciences.

[16]  E. Grell,et al.  Carriers and specificity in membranes. IV. Model vesicles and membranes. The formation of asymmetrical spherical lecithin vesicles. , 1971, Neurosciences Research Program bulletin.

[17]  R. Dowben,et al.  Formation and properties of thin‐walled phospholipid vesicles , 1969, Journal of cellular physiology.

[18]  S. Razin Reconstruction of biological membranes. , 1972, Biochimica et biophysica acta.

[19]  D. Papahadjopoulos,et al.  Phospholipid model membranes. I. Structural characteristics of hydrated liquid crystals. , 1967, Biochimica et biophysica acta.

[20]  Y. Rustum,et al.  Inhibition of tumor cell growth in vitro and in vivo by 1-beta-D-arabinofuranosylcytosine entrapped within phospholipid vesicles. , 1976, Cancer research.

[21]  D. Deamer,et al.  Large volume liposomes by an ether vaporization method. , 1976, Biochimica et biophysica acta.