High drug:lipid formulations of liposomal antineoplastic agents

Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Liposomes

Patent

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

264 43, 424 121, 436164, 436829, 514908, A61K 9127, A61K 9133

Patent

active

056163410

ABSTRACT:
A method for encapsulation of antineoplastic agents in liposomes is provided, having preferably a high drug:lipid ratio. Liposomes may be made by a process that loads the drug by an active mechanism using a transmembrane ion gradient, preferably a transmembrane pH gradient. Using this technique, trapping efficiencies approach 100%, and liposomes may be loaded with drug immediately prior to use, eliminating stability problems related to drug retention in the liposomes. Drug:lipid ratios employed are about 3-80 fold higher than for traditional liposome preparations, and the release rate of the drug from the liposomes is reduced. An assay method to determine free antineoplastic agents in a liposome preparation is also disclosed.

REFERENCES:
patent: 3962429 (1976-06-01), Furuno et al.
patent: 3993754 (1976-11-01), Rahman et al.
patent: 4145410 (1979-03-01), Sears
patent: 4193983 (1980-03-01), Ullman et al.
patent: 4217344 (1980-08-01), Vanlerberghe et al.
patent: 4224179 (1980-09-01), Schneider et al.
patent: 4235871 (1980-11-01), Papahadjopoulos et al.
patent: 4241046 (1980-12-01), Papahadjopoulos et al.
patent: 4372949 (1983-02-01), Kodama et al.
patent: 4389330 (1983-06-01), Tice et al.
patent: 4411894 (1983-10-01), Schrank et al.
patent: 4419348 (1983-12-01), Rahman et al.
patent: 4438052 (1984-03-01), Weder et al.
patent: 4460577 (1984-07-01), Moro et al.
patent: 4460689 (1984-07-01), Foor et al.
patent: 4485045 (1984-11-01), Regan
patent: 4515736 (1985-05-01), Deamer
patent: 4522803 (1985-06-01), Lenk et al.
patent: 4551288 (1985-11-01), Kelly
patent: 4587240 (1986-05-01), Hider et al.
patent: 4588578 (1986-05-01), Fountain et al.
patent: 4619794 (1986-10-01), Hauser
patent: 4622188 (1986-11-01), Adamich et al.
patent: 4721612 (1988-01-01), Janoff et al.
patent: 4737323 (1988-04-01), Martin et al.
patent: 4769250 (1988-09-01), Forssen
patent: 4883665 (1989-11-01), Miyazima et al.
patent: 5047245 (1991-09-01), Bally et al.
patent: 5077056 (1991-12-01), Bally et al.
patent: 5082664 (1992-01-01), Lenk et al.
Mayer et al.: "Influence of Vesicle Size, Lipid Composition, and Drug-to-Lipid Ratio on the Biological Activity of Liposomal Doxorubicin in Mice", Cancer Res. 49:5922-5930 (1989).
U.S. application No. 220,388, Mehlhorn, filed Jul. 12, 1988.
U.S. application No. 122,354, Forssen, filed Nov. 18, 1987.
Crommelin, et al., "Preparation and characterization of doxorubicin-containing liposomes, II. Loading capacity, long-term stability and doxorubicin-bilayer interaction mechanism", Chemical Abstracts, vol. 100, 1984, Abs. 109032w.
Garcia, et al.; "Mechanism of lactose translocation in proteoliposomes reconstituted with lac carrier protein prified from Escherishia coli", Biol. Abs. vol. 77(7):6013, 1984, Abs. 54638.
Groom, et al., "Liposomes", Chemical Abstracts, vol. 102, 1985, Abs #67398d.
Kirby, et al., "Dehydration-rehydration vesicles: a simple method for high yield drug entrapment in liposomes", Chemical Abstracts,. vol. 102, 1985, Abs #84326w.
Moro, et al., "Purification of Liposome Suspensions", Chemical. Abstracts,. vol. 94, 1981, p. 372, Abs. 52931g.
Shakov, et al., "Reconstitution of highly purified proton-translocating pyrophosphatase from Rhodospirillum rubrum", Biol. Abs. 77(12):10459, 1984, Abs. 94506.
Van Hoesel, et al., "Reduced cardiotoxicity and nephrotoxicity with preservation of anittumor activity of Doxorubicin entrapped in stable liposomes in the LOU/M", Chemical. Abstracts,. vol. 101, 1984, 163307y.
Rosa, et al.; "Absorption and Tissue Distribution of Doxorubicin Entrapped in Liposomes following Intravenous or Intraperitoneal administration:", 1983; Pharmacol. 25:221-229.
Ryman, et al., "Liposomes--Further Considerations of Their Possible Role as Carriers of Therapeutic Agents", 1983; Targeting of Drugs, pp. 235-248.
Shinozawa, et al., "Tissue Distribution and Antitumor Effect of Liposome-Entrapped Doxorubicin (Adriamycin) in Ehrlich Solid Tumor-Bearing Mouse", 1981; Acta. Med. Okayama, 35:395-405.
Szoka, Jr., et al., "Comparative Properties and Methods of Preparation of Lipid Vesicles (Liposomes)", 1980; Ann. Rev. Biophys. Bioeng. 9:467-509.
Crommelin, et al., "Preparation and characteriation of doxorubicin-containing liposomes: I. Influence of liposome charge and pH of hydration medium on loading capacity and particle size", Int. J. Pharms, 16, (1983), 79-92.
Kornberg, et al., "Measurement of Transmembrane Potentials in Phospholipid Vesicles", 1972, Proc. Nat. Aca. Sci. USA 69(6), pp. 1508-1513.
Layton, et al.; "A Comparison of the Therapeutic Effects of Free and Liposomally Encapsulated Vincristine in Leukemic Mice", 1980; Europe. J. Cancer., vol. 16, 945-950.
Lopez-Berestein, et al., "Liposomal Amphotericin B For the Treatment of Systemic Fungal Infections in Patients with Cancer: A Preliminary Study", 1985; J. Infect. Dis., 151:704-710.
Mayer, et al.; "Solute distributions an trapping efficiencies observed in freeze-thawed multilamellar vesicles", 1985; Biochim. Biophys. Acta., 187:193-196.
Mayer, et al., "Uptake of antineoplastic agents into large unilamellar vesicles in response to a membrane potential", 1985; Biochem. Biophys. Acta., 816:294-302.
Mayer, et al., "Uptake of adriamycin into large unilamellar vesicles in response to a pH gradient", 1986; Biochim. Biophys. Acta., 857:123.
Minow, et al., "Adriamycin (NSC-123127) Cardiomyophathy--An Overview With Determination of Risk Factors", 1975; Cancer Chemother. Rep. 6: 195-201.
Nichols and Deamer, "Catecholamine Uptake and Concentration by Liposomes Maintaining pH Gradients" 1976, BBA 455, pp. 269-271.
Olson, et al., "Characterization, Toxicity and Therapeutic Efficacy of Adriamycin Encapsulated in Liposomes", 1982; Br. J. Cancer Clin. Oncol., 18-167.
Papahadjopoulos, et al., "Phospholipd Model Membranes", 1967: Biochim. Biophys. Acta., 135:624-638.
Rahman, et al., "Doxorubicin-induced Chronic Cardiotoxicity and its Protection by Liposomal Administration", 1982; Cancer Res. 42:1817.
Rahman, et al., "Liposomal Protection of Adriamycin-induced Cardiotoxicity in Mice", 1980; Cancer Res. 40:1532-1536.
Rahman, et al., "Pharmacological, Toxicological, and Therapeutic Evaluation in Mice of Doxorubicin Entrapped in Cardiolipid Liposomes", 1985; Cancer Res. 45:796-803.
Richardson, et al., "Tissue Distribution and Tumour Localization of 99m-Technetium-Labeled Liposomes in Cancer Patients", 1979; Br. J. Cancer 40:35-43.
Rosa, et al., in Transport in Biomembranes: Model Systems and Reconstitution, R. Antolini ed., "Liposomes Containing Doxorubicin: An Example of Drug Targeting", 1982; pp. 243-256.
Crommelin et al; Chem. Abs. vol. 99, 1983, Abs #128259c.
Bangham, et al.; "Diffusion of Univalent Iona Across the Lamellae of Swollen Phospholipids", 1965; J. Mol. Biol., 13:238-252.
Bartlett, et al.; "Phosphorus Assay in Column Chromatography", 1959; J. Bio. Chem. 234:466-468.
Casey et al.; "Active Proton Uptake by Chromaffin Granules: Observation by Amine Distribution and Phosphorus-31 Nuclear Magnetic Resonance Techniques" 1977, Biochemistry 16(5), pp. 972-976.
Cramer and Prestegard, "NMR Studies of pH-Induced Transport of Carboxylic Acids Across Phopholipid Vesicle Membranes", Biochem. Biophys. Res. Commun. 1977.
Deamer, et al., "The response to Fluorescent Amine to pH Gradients Across Liposome Membranes", 1972, Biochim. Biophys, Acta, 274, pp. 323-335.
Forssen, et al., "Improved Therapeutic Benefits of Doxorubicin by Entrapment in Anionic Liposomes", 1983; Cancer Res. 43:546-550.
Gabizon, et al.; "Liposomes as In Vivo Carriers of Adriamycin: Reduced Cardiac Uptake and Preserved Antitumor Activity in Mice", 1982; Cancer Res. 42:4734-4739.
Gabizon, et al., "Enhancement of Adriamycin Delivery to Liver Metastatic Cells with Increased Tumoricidal Effect Using Liposomes as Drug Carriers", 1983; Cancer Res. 43:4730-4735.
Gannphati, et al., "Effect of cholesterol content of liposomes on the encapsulation, efflux and toxicity of adriamycin", 1984; Biochem. Pharmacol. 33:698-700.
Gregoriadis, "Targeting of Drugs: Implications of Medicine", 1981;The Lancet, 241-247.
Herman, et al., "Prevention of Chronic Doxorubicin Cardio

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

High drug:lipid formulations of liposomal antineoplastic agents does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with High drug:lipid formulations of liposomal antineoplastic agents, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and High drug:lipid formulations of liposomal antineoplastic agents will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-537141

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.