Liposomes with enhanced circulation time and method of treatment
First Claim
1. A liposome composition for use in localizing a compound in a solid tumor via the bloodstream comprising, liposomes (i) composed of vesicle-forming lipids and between 1-20 mole percent of an amphipathic vesicle-forming lipid derivatized with a hydrophilic polymer, and (ii) having a selected mean particle diameter in the size range between about 0.07-0.12 microns, and the compound in liposome-entrapped form.
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Abstract
A liposome composition for localizing an anti-tumor compound to a solid tumor via the bloodstream. The liposomes, which contain the agent in entrapped form, are composed of vesicle-forming lipids and between 1-20 mole percent of a vesicle-forming lipid derivatized with hydrophilic biocompatible polymer, and have sizes in a selected size range between 0.07 and 0.12 microns. After intravenous administration, the liposomes are taken up by the tumor within 24-48 hours, for site-specific release of entrapped compound into the tumor. In one composition for use in treating a solid tumor, the compound is an anthracycline antibiotic drug which is entrapped in the liposomes at a concentration of greater than about 50 μg agent/μmole liposome lipid. The method results in regression of solid colon and breast carcinomas which are refractory to anthracycline antibiotic drugs administered in free form or entrapped in conventional liposomes.
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Citations
20 Claims
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1. A liposome composition for use in localizing a compound in a solid tumor via the bloodstream comprising,
liposomes (i) composed of vesicle-forming lipids and between 1-20 mole percent of an amphipathic vesicle-forming lipid derivatized with a hydrophilic polymer, and (ii) having a selected mean particle diameter in the size range between about 0.07-0.12 microns, and the compound in liposome-entrapped form.
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7. A liposome composition for use in localizing an anthracycline anti-tumor drug in a solid tumor via the bloodstream comprising,
liposomes (i) composed of vesicle-forming lipids and between 1-20 mole percent of an amphipathic vesicle-forming lipid derivatized with polyethyleneglycol, and (ii) having an average size in a selected size range between about 0.07-0.12 microns, and the drug, at least about 80% in liposome-entrapped form, and having a concentration in the liposomes is greater than 50 μ - g agent/μ
mole liposome lipid. - View Dependent Claims (8)
- g agent/μ
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9. For use in localizing a compound in a solid tumor by IV administration of the agent, a liposome composition characterized by:
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(a) liposomes composed of vesicle-forming lipids and between 1-20 mole percent of an amphipathic vesicle-forming lipid derivatized with a hydrophilic polymer, (b) a blood lifetime, as measured by the percent of a liposomal marker present in the blood 24 hours after intravenous administration which is several times greater than that of liposomes in the absence of the derivatized lipids;
(c) an average liposome size in a selected size range between about 0.07-0.12 microns, and (d) the compound in liposome-entrapped form. - View Dependent Claims (10, 11, 12)
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13. For use in treating a solid tumor by intravenous administration of an anthracycline antibiotic drug, a liposome composition characterized by:
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(a) liposomes composed of vesicle-forming lipids and between 1-20 mole percent of an amphipathic vesicle-forming lipid derivatized with a polyethyleneglycol, (b) a blood lifetime, as measured by the percent of a liposomal marker present in the blood 24 hours after IV administration which is several times greater than that of liposomes in the absence of the derivatized lipids;
(c) an average liposome size in a selected size range between about 0.07-0.12 microns, (d) at least about 80% of the drug in liposome-entrapped form, and (c) a concentration of drug in the liposomes of at least about 50 μ
g drug/μ
mole lipid.
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14. A method of preparing an agent for localization in a solid tumor, when the agent is administered by IV injection, comprising
entrapping the agent in liposomes which are characterized by: -
(a) a composition which includes between 1-20 mole percent of an amphipathic vesicle-forming lipid derivatized with a hydrophilic polymer, and (b) an average liposome size in a selected size range between about 0.07-0.12 microns. - View Dependent Claims (15, 16)
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17. A method of localizing a compound in a solid tumor in a subject comprising,
preparing a composition of liposomes (i) composed of vesicle-forming lipids and between 1-20 mole percent of an amphipathic vesicle-forming lipid derivatized with a hydrophilic polymer, (ii) having an average size in a selected size range between about 0.07-0.12 microns, and (iii) containing the compound in liposome-entrapped form, and injecting the composition intravenously in the subject in an amount effective to localize a therapeutically effective quantity of the agent in the solid tumor.
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19. A method of treating a breast or colin carcinoma in a subject with an anthracycline antibiotic drug, comprising comprising
entrapping the drug in liposomes (i) composed of vesicle-forming lipids and between 1-20 mole percent of an amphipathic vesicle-forming lipid derivatized with a hydrophilic polymer, and (ii) having an average size in a selected size range between about 0.07-0.12 microns, at a concentration of entrapped agent of greater than about 50 μ - g agent/μ
mole liposome lipid, with at least about 80% of the agent entrapped in the liposomes, andinjecting the composition intravenously in the subject in an amount effective to localize a therapeutically effective quantity of the agent in the carcinoma. - View Dependent Claims (20)
- g agent/μ
Specification