Solid tumor treatment method and composition
First Claim
1. A liposome composition for use in localizing a compound in a solid tumor via the bloodstream, by liposome extravasation into the tumor, comprisingliposomes (i) composed of vesicle-forming lipids and between 1-20 mole percent of an amphipathic vesicle-forming lipid derivatized with a hydrophilic polymer selected from the group consisting of polyethyleneglycol, polylactic acid, polyglycolic acid and polylactic acid/polyglycolic acid copolymers, and (ii) having a selected mean particle diameter in the size range between about 0.07 to 0.12 microns, andthe compound in liposome-entrapped form,and characterized by a liposome blood lifetime, 24 hours after intravenous injection, that is several times greater than the blood lifetime of liposomes in the absence of the derivatized lipid.
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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
15 Claims
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1. A liposome composition for use in localizing a compound in a solid tumor via the bloodstream, by liposome extravasation into the tumor, 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 selected from the group consisting of polyethyleneglycol, polylactic acid, polyglycolic acid and polylactic acid/polyglycolic acid copolymers, and (ii) having a selected mean particle diameter in the size range between about 0.07 to 0.12 microns, and the compound in liposome-entrapped form, and characterized by a liposome blood lifetime, 24 hours after intravenous injection, that is several times greater than the blood lifetime of liposomes in the absence of the derivatized lipid.
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7. A liposome composition for use in localizing an anthracycline anti-tumor drug in a solid tumor via the bloodstream by liposome extravasation into the tumor, 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 to 0.12 microns, and the drug, at least about 80% in liposome-entrapped form, and having a concentration in the liposomes greater than 50 μ - g agent/μ
mole liposome lipid,and characterized by a liposome blood lifetime, 24 hours after intravenous injection, that is several times greater than the blood lifetime of liposomes in the absence of the derivatized lipid. - View Dependent Claims (15)
- g agent/μ
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8. A method of preparing an agent for localization in a solid tumor by extravasation of liposomes containing the agent into the solid tumor, when the agent is administered by IV injection, comprising
entrapping the agent in liposomes which are characterized by: -
(a) a lipid composition which includes between 1-20 mole percent of an amphipathic vesicle-forming lipid derivatized with a hydrophilicpolymer selected from the group consisting of polyethyleneglycol, polylactic acid, polyglycolic acid and polyactic acid/polyglycolic acid copolymers, (b) an average liposome size in a selected size range between about 0.07-0.12 microns; and (c) a liposome blood lifetime 24 hours after intravenous injection, that is several times greater than the blood lifetime of liposomes in the absence of the derivatized lipid. - View Dependent Claims (9, 10)
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11. A method of localizing a compound in a solid tumor in a subject by extravasation of liposomes containing the agent into the solid tumor 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 selected from the group consisting of polyethyleneglycol, polylactic acid, polyglycolic acid and polylactic acid/polyglycolic acid copolymers, said liposomes having a blood lifetime, as measured by the percent of a liposome marker present in the blood 24 hours after intravenous administration, which is several times greater than that of liposomes in absence of the derivatized lipids, (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, injecting the composition intravenously in the subject in an amount effective to localize a therapeutically effective quantity of the agent in the solid tumor, and by said injecting, achieving a localization of the liposomes in the solid tumor, 48 hours after intravenous administration, that is substantially greater than that of liposomes in the absence of the derivatized lipid.
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13. A method of treating breast or colon carcinoma in a subject with an anthracycline antibiotic drug, 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 selected from the group consisting of polyethyleneglycol, polylactic acid, polyglycolic acid and polylactic acid/polyglycolic acid copolymers, said liposomes having a blood lifetime, as measured by the percent of a liposome marker present in the blood 24 hours after intravenous administration, which is several times greater than that of liposomes in absence of the derivatized lipids, and (ii) having an average size in a selected size range between about 0.07-0.12 microns at a concentration of entrapped drug of greater than about 50 μ - g drug/μ
mole liposome lipid, with at least about 80% of the drug 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 (14)
- g drug/μ
Specification