Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Liposomes
Patent
1996-01-29
2000-08-29
Page, Thurman K.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Liposomes
424400, 935 54, A61K 9127
Patent
active
061104906
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention is directed to a liposomal preparation which is based on a composition of specific lipids which form liposomes. It is also an object of the present invention to provide a method for preparing a liposomal composition carrying a biologically active agent which is simple and very efficient. The liposomal delivery system of the present invention is used as a highly efficient transfer therapy method.
BACKGROUND OF THE INVENTION
Lipidic particles have been shown to be efficient vehicles for many in vitro and in vivo applications. Lipidic particles complexed with DNA have been used in vitro (Felgner P. L., et al. Proc. Natl. Acad. Sci. USA 84, 7413-7417 (1987); Gao X. et al. Biochem. Biophys. Res. Commun. 179, 280-285 (1991)) and in vivo (Nabel E. G., et al. Science 249, 1285-1288 (1990); Wang C. et al. Proc. Natl. Acad. Sci. USA 84, 7851-7855 (1987); Zhu N., et al. Science 261, 209-211 (1993); Soriano P., et al. Proc. Natl. Acad. Sci. USA 80, 7128-7131 (1983)) for the expression of a given gene through the use of plasmid vectors. Formation of complexes of DNA with cationic lipidic particles has recently been the focus of research of many laboratories. In particular, lipofectin.TM. (Gibco BRL, Gaithersburg, Md.) has been successfully used for the transfection of various cell lines in vitro (Felgner P. L., et al. Proc. Natl. Acad. Sci. USA 84, 7413-7417 (1987)) and for systemic gene expression after intravenous delivery into adult mice (Zhu N., et al. Science 261, 209-211 (1993)).
Lipidic particles may be complexed with virtually any biological material. These particles may be complexed with proteins, therapeutic agents, chemotherapeutic agents, and nucleic acids and provide a useful delivery system for these agents. One such drug delivery system, gene therapy, is one such area which has produced promising results. In this area two different strategies have emerged: Gene therapy and oligonucleotide-based therapeutics. To be successful these two approaches must be mediated by an efficient "in vivo" transfer of the nucleic acid material to the target cells and there is a need to provide an efficient and safe delivery system of nucleic materials.
Gene therapy may involve the transfer of normal, functional genetic material into cells to correct an abnormality due to a defective or deficient gene product. Typically, the genetic material to be transferred should at least contain the gene to be transferred together with a promoter to control the expression of the new gene.
Viral agents have been demonstrated to be highly efficient vectors for the transfection of somatic cells. Retroviruses in particular have received a great deal of attention because they not only enter cells efficiently, but also provide a mechanism for stable integration into the host genome through the provirus. However, clinical use of retroviral vectors is hampered by safety issues. A first concern is the possibility of generating an infectious wild type virus following a recombination event. A second concern is the consequences of the random integration of the viral sequence into the genome of the target cell which may lead to tumorigenic event. In addition, as retroviruses would only complete their life cycle in dividing cells, a retroviral vector would be inefficient in targeting cells which are not dividing. DNA viruses such as adenoviruses are potential gene carriers but this strategy is limited in the size of the foreign DNA adenoviruses can carry and because of the restricted host range. However, the advantage of adenoviruses over retroviral vectors is their ability to infect post-mitotic cells.
Synthetic gene-transfer vectors have been subject to intense investigation since this strategy appears to be clinically safe. Potential methods of gene delivery that could be employed include DNA/protein complexes (Cristiano R. J., et al. Proc. Natl. Acad. Sci. USA 90, 2122-2126 (1993)) or lipidic particles (Nabel E. G., et al. Science 249, 1285-1288 (1990); Felgner P. L., et al. Proc. Natl. Acad. Sci.
REFERENCES:
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patent: 5283185 (1994-02-01), Epand
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Felgner PNAS 84, p. 7413 Nov. 1987.
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Page Thurman K.
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