Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Liposomes
Patent
1995-11-16
1998-02-10
Kishore, Gollamudi S.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Liposomes
424489, 424490, 424502, 4241841, 4241881, 4242041, 4242081, 4242341, 4242371, 4242361, 4242691, 428937, 514937, A61K 9127, A61K 916
Patent
active
057166374
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention concerns methods and compositions for delivery of vaccines by parenteral and other routes of administration. More particularly, it concerns stable lipid-in-water nanoemulsions or emulsomes containing small lipid particles which are useful as delivery vehicles for both hydrophilic and lipophilic immunogens enhancing their immunogenicity and improving their immune response.
BACKGROUND OF THE INVENTION
The body's immune system recognizes pathogens as foreign and is thought to produce antibodies to them by two main pathways. In one pathway, antigens on the pathogen surface presumably bind to receptor molecules on the white blood cells known as B cells, causing them to become plasma cells, which proliferate and secrete antibodies specific for the pathogen. In the second pathway, circulating macrophages bind to the pathogens, endocytose them, and display processed antigens on their surface.
T cells then bind to the expressed antigen and by way of several complex steps this binding ultimately results in further plasma cell proliferation and increased antibody production.
In the past, the risks of whole-pathogen vaccines and limited supplies of useful antigens posed barriers to development of practical vaccines. Today, the tremendous advances of genetic engineering and the ability to obtain many synthetic recombinant protein antigens derived from parasites, viruses, and bacteria has revolutionized the development of new generation vaccines.
Although the new, small synthetic antigens offer advantages in the selection of antigenic epitopes and safety, a general drawback of small antigens is poor immunogenicity.
Unfortunately, the body's immune system does not respond strongly to small peptides. In particular, macrophages do not readily ingest and process the small antigens resulting in low antibody titers and the need for repeated immunizations. This lack of immunogenicity has created an acute need to identify pharmaceutically acceptable delivery systems for these new antigens.
Several reports describing the improvement of immune response achieved by the association of antigens with lipid carriers such as liposomes or microparticles like polymeric biodegradable microcapsules have been published (C. R. Alving, Liposomes as Carriers of Vaccines, in "Liposomes: From Biophysics to Therapeutics", M. J. Ostro, ed., Ch. 6, Marcel Dekker Inc., New York, 1987, pp. 195-218; J. H. Eldridge et al, Molec. Immunol., 28, 287, 1991). The ability of these delivery systems to enhance immunogenicity was related to the physicochemical characteristics of the particles.
When antigens are incorporated in lipid carriers by encapsulation or entrapment, or embedded in their surface, they show enhanced ability to evoke a strong immune response. Vaccines formulated in lipid carriers probably enhance antibody production by increasing activity along both pathways of stimulation of immune system described above. When multiple antigens attached to a lipid carrier bind to multiple receptors on a B cell, the resulting plasma cell probably proliferates faster than it does when it encounters a solitary antigen. Similarly, whereas a macrophage is unlikely to phagocytase a small antigen efficiently, it will readily digest a lipid carrier particle containing the antigen. When phagocytosis takes place, antigens ooupled to the surface of the lipid carrier or encapsulated within the particle are ingested and possibly displayed as processed antigen on the macrophage surface. Such antigen presentation could result in T cell activation and additional plasma cell proliferation and increased antibody production.
Most vaccine adjuvants are also surface-active, or have a special surface interface. Surface-active agents concentrate at the surface formed by the interface of water and non-polar substances such as lipid or lipid membrane. Most adjuvants are also water-insoluble surfactants, so lipoidal vehicles are necessary for proper delivery of the antigen.
The use of liposomes as drug delivery systems has been known
REFERENCES:
patent: 4880635 (1989-11-01), Janoff
patent: 5023271 (1991-06-01), Vigne
patent: 5171737 (1992-12-01), Weiner
patent: 5188837 (1993-02-01), Domb
patent: 5284663 (1994-02-01), Speaker
patent: 5302401 (1994-04-01), Livesidge
patent: 5306508 (1994-04-01), Kossovsky
patent: 5308624 (1994-05-01), Maircent
patent: 5576016 (1996-11-01), Amselem
CRC Press, Inc., Liposome Technology, 2nd Edition, vol. 1, Chapter 28, p. 1, Liposome Preparation and Related Techniques, edited by Gregory Gregoiadis, Ph.D., "A Large-Scale Method For the Preparation Of Sterile And Nonpyrogenic Liposomal Formulations Of Defined Size Distributions For Clinical Use", Shimon Amselem, Alberto Gabizon, and Yechezkel Barenholz.
Methods of Biochemical Analysis, vol. 33, D. Glick, editor, J. Wiley & Sons, N.Y., 1988, "Liposomes: Preparation, Characterization, and Preservation", Dov Lichtenberg and Yechezkel Barenholz.
Journal of Pharmaceutical Sciences, vol. 79, No. 12, Dec. 1990, "optimization and Upscaling of Doxorubicin-Containing Liposomes for Clinical Use", S. Amselem, A. Gabizon and Y. Barenholz.
CRC Press, Inc., 1993, Liposome Technology, 2nd Ed., edited by G. Gregoriadis, Ph.D., vol. 1, Chapter 3, p. 49, "Liposome Preparation Using High-Pressure Homogenizers", Martin M. Brandi, Bieter Bachmann, Markus Drechsler, and Kurt H. Bauer.
Elsevier Science Publishers B.V. (Biomedical Division, 1986, Laboratory Techniques in Biochemistry and Molecular Biology, vol. 3, part 2, edited by R.H. Burdon and P.H. van Knippenbert, "Techniques of Lipidology -- Isolation, Analysis and Identification of Lipids", 2nd revision edition, Moris Kates.
Prog. Lipd Res., vol. 31, No. 4 pp. 345-372, 1992, "Recent Aspects in the Use Of Liposomes in Biotechnology and Medicine" by Toshinori Sato et al.
Vol. 6, p. 195, "Liposomes As Carrier for Vaccines" by Carl R. Alving -- Walter Reed Army Institute of Research, Washinton, D.C.
American Chemical Society, vol. 18, No. 19, 1979, p. 4169, "Dependence of the Conformation of the Polar Head Groups of Phosphatidycholine on Its Packing in Bilayers. Nuclear Magnetic Resonance Studies on the Effect of the Binding of Lanthanide Ions" by Dov Lichtenberg et al.
Proc. Natl. Acad. Sci. USA, vol. 89, pp. 358-362, Jan. 1992, Immunology -- "Liposomal malaria vaccine in humans: A safe and potent adjuvant strategy" by Louis F. Fries et al.
Anselem Shimon
Aviv Haim
Friedman Doron
Lowell George H.
Kishore Gollamudi S.
Pharmos Corporation
The United States of America as represented by the Secretary of
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