# US 7,744,921 B2 · Liposome loading with metal ions > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 7,744,921 B2 - Document ID: US7744921B2 - Status: Granted - Kind: B2 - Application number: 11/842,130 - Filed: 2007-08-20 - Published: 2008-02-21 - Granted: 2010-06-29 - Earliest claimed: 2001-10-03 - Assignees: Celator Pharmaceuticals, Inc. - Inventors: Paul Tardi; Sharon Johnstone; Murray Webb; Marcel Bally; Sheela Abraham - Web page: https://patentgrep.com/patent/US7744921B2 ## CPC - A61K 31/7072: having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine - A61K 9/127: Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant - A61K 9/1271: Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911}) - A61K 9/1272: comprising non-phosphatidyl surfactants as bilayer-forming substances, e.g. cationic lipids or non-phosphatidyl liposomes coated or grafted with polymers (lipids as modifying agents {A61K47/543}) - A61K 31/00: Medicinal preparations containing organic active ingredients - A61K 31/4745: condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48) - A61K 31/704: attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)} - A61K 31/7048: having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin} - A61K 31/7076: containing purines, e.g. adenosine, adenylic acid - A61K 33/243: Platinum; Compounds thereof - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 35/00: Antineoplastic agents - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract This invention relates to encapsulation of drugs and other agents into liposomes. ## Claims ### Claim 1 A method of loading at least one therapeutic agent into a liposome in a liposome composition, the method comprising: i) providing a composition comprising liposomes, said liposomes lacking an ionophore, in an external solution, the liposomes containing an internal copper-ion compatible solution comprising encapsulated copper ions; ii) adding at least one therapeutic agent to the external solution; and iii) maintaining the agent in the external solution for sufficient time to load the agent into the liposomes, whereby said copper or cobalt ions effect said loading; wherein the external solution and external surfaces of the liposome contain substantially no uncomplexed copper ions; and wherein the liposomes comprise 0-20 mol % cholesterol. ### Claim 2 (depends on 1) The method of claim 1, wherein the external solution comprises a copper chelating agent. ### Claim 3 (depends on 1) The method of claim 1, wherein uncomplexed copper ions are removed from the external solution prior to step (ii) by chromatography or by extensive solution exchange or dialysis. ### Claim 4 (depends on 1) The method of claim 1, wherein the internal solution and the external solution have substantially the same pH. ### Claim 5 (depends on 1) The method of claim 1, wherein the pH of the internal solution is in the range of about 6.0 to about 8.5. ### Claim 6 (depends on 1) The method of claim 1, wherein the liposomes comprise one or more lipids that are negatively charged at physiological pH. ### Claim 7 (depends on 6) The method of claim 6, wherein the one or more negatively charged lipids are selected from PG and PI. ### Claim 8 (depends on 1) The method of claim 1, wherein a second therapeutic agent is loaded by means of a transmembrane gradient established with an ionophore supplied to the liposomes after step (iii). ### Claim 9 A method of loading at least one therapeutic agent into a liposome in a liposome composition, the method comprising: i) providing a composition comprising liposomes in an external solution, the liposomes containing an internal copper-ion compatible solution comprising encapsulated copper ions; ii) adding at least one therapeutic agent to the external solution; and iii) maintaining the agent in the external solution for sufficient time to load the agent into the liposomes, wherein the external solution and external surfaces of the liposome contain substantially no uncomplexed copper ions; and wherein the liposomes comprise 0-20 mol % cholesterol; and wherein the liposomes do not at any time during said loading comprise an ionophore, whereby said copper ions effect said loading. ### Claim 10 A method of loading at least one therapeutic agent into a liposome in a liposome composition, the method comprising: i) providing a composition comprising liposomes in an external solution, the liposomes containing an internal copper-ion compatible solution comprising encapsulated copper ions; ii) adding at least one therapeutic agent to the external solution; and iii) maintaining the agent in the external solution for sufficient time to load the agent into the liposomes, wherein the external solution and external surfaces of the liposome contain substantially no uncomplexed copper ions; and wherein the liposomes comprise 0-20 mol % cholesterol; and wherein said loading is conducted in the absence of ionophore, whereby the therapeutic agent is encapsulated at levels greater than those achieved in the absence of said copper ions.