Microreservoir liposome composition and method

A liposome composition effective to extend, to at least 48 hours, the period of therapeutic activity of a polypeptide which can be administered intravenously in a therapeutically effective amount, which is cleared in free form from the bloodstream with a halflife of less than about 4 hours, and whose therapeutically active blood concentration is in the picogram-nanogram/ml concentration range, comprising

• liposomes (i) composed of vesicle-forming lipids and between 1-20 mole percent of a vesicle-forming lipid derivitized with a polymer selected from the group consisting of polyethyleneglycol, polyacetic acid and polyglycolic acid, and (ii) having a selected mean particle diameter in the size range between about 0.1 to 0.4 microns, and
• the polypeptide in liposome-entrapped form,
• for intravenous administration at a dose of the composition which contains an amount of the polypeptide liposome-entrapped form which is at least three times such therapeutically effective amount.

A method of extending, to at least 24 hours, the period of effective activity of a therapeutic compound which can be administered intravenously in a therapeutically effective amount, and which has a halflife in the bloodstream in free form of less than about 4 hours, comprising

• providing a liposome composition containing liposomes (i) composed of vesicle-forming lipids and between 1-20 mole percent of a vesicle-forming lipid derivitized with ah polymer selected from the group consisting of polyethyleneglycol, polyacetic acid and polyglycolic acid, and (ii) having a selected mean particle diameter in the size range between about 0.1 to 0.4 microns, and the compound at least about 70% in liposome-entrapped form, and
• administering the liposome composition intravenously to a subject at a dose which contains an amount of the compound which is at least three times such therapeutically effective amount.

A liposome composition effective to extend, to at least one week, the period of effective activity of a therapeutic compound which can be administered in a therapeutically effective amount, comprising

• liposomes (i) composed of vesicle-forming lipids and between 1-20 mole percent of a vesicle-forming lipid derivitized with a polymer selected from the group consisting of polyethyleneglycol, polyacetic acid and polyglycolic acid, and (ii) having a selected mean particle diameter in the size range between about 0.1 to 0.4 microns, and
• the compound in liposome-entrapped form,
• for subcutaneous administration at a dose of the composition which contains an amount of the compound in liposome-entrapped form which is at least ten times such therapeutically effective intravenously administered amount.

A method of extending, to at least one week, the period of effective activity of a therapeutic compound which can be administered in a therapeutically effective amount, comprising

• providing a liposome composition containing liposomes (i) composed of vesicle-forming lipids and between 1-20 mole percent of a vesicle-forming lipid derivitized with a polymer selected from the group consisting of polyethyleneglycol, polyacetic acid and polyglycolic acid, and (ii) having a selected mean particle diameter in the size range between about 0.1 to 0.4 microns, and the compound at least about 70% in liposome-entrapped form, and
• administering the composition subcutaneously to a subject at a dose which contains an amount of the compound in liposome-entrapped form which is at least ten times such therapeutically effective intravenously administered amount.

A liposome composition composed of vesicle-forming lipids and a vesicle-forming lipid derivatized with a hydrophilic polymer selected from the group consisting of polylactic acid and polyglycolic acid.

A lipid composition composed of a vesicle-forming lipid having a polar head group, and a polylactic acid moiety derivatized to said head group.

A lipid composition composed of a vesicle-forming lipid having a polar head group, and a polyglycolic acid moiety derivatized to said head group.