Combinational liposome compositions for cancer therapy

Patent metadata

Field	Value
Publication number	US-9370489-B2
Application number	US-201213664457-A
Country	US
Kind code	B2
Filing date	Oct 31, 2012
Priority date	Oct 31, 2011
Publication date	Jun 21, 2016
Grant date	Jun 21, 2016

Abstract

The present invention provides methods for delivery of therapeutic agents to a subject using multi-component liposomal systems. The methods include administration of a therapeutic liposome containing an active agent, followed by a administration of an attacking liposome that induces release of the agents from the therapeutic liposome.

First claim

What is claimed is:

1. A method for delivering a therapeutic agent to a subject, the method comprising:
a) administering to the subject a liposome comprising a therapeutic agent; and
b) administering to the subject a lipid nanoparticle comprising a non-ionic triggering agent;

whereby release of the therapeutic agent from the liposome following administration of the lipid nanoparticle is increased, relative to the release of the therapeutic agent from the liposome without administration of the lipid nanoparticle.

2. The method of claim 1 , wherein the liposome comprises one or more lipids selected from the group consisting of a phospholipid, a steroid, and a cationic lipid.

3. The method of claim 2 , wherein the phospholipid is selected from a phophatidylcholine, a phosphatidylglycerol, a phosphatidylethanolamine, a phosphatidylserine, a phosphatidylinositol, and a phosphatidic acid.

4. The method of claim 3 , wherein the phosphatidylcholine is DSPC.

5. The method of claim 3 , wherein the phosphatidylglycerol is DSPG.

6. The method of claim 3 , wherein the phosphatidylethanolamine is DSPE-PEG(2000).

7. The method of claim 2 , wherein the steroid is cholesterol.

8. The method of claim 1 , wherein the lipid nanoparticle is selected from the group consisting of a second liposome, a micelle, and mixtures thereof.

9. The method of claim 8 , wherein the lipid nanoparticle is a second liposome.

10. The method of claim 9 , wherein the second liposome comprises one or more lipids selected from the group consisting of a phospholipid, a steroid, and a cationic lipid.

11. The method of claim 10 , wherein the phospholipid is selected from a phophatidylcholine, a phosphatidylglycerol, a phosphatidylethanolamine, a phosphatidylserine, a phosphatidylinositol, and a phosphatidic acid.

12. The method of claim 11 , wherein the phosphatidylcholine is DPPC.

13. The method of claim 10 , wherein the steroid is cholesterol.

14. The method of claim 10 , wherein the cationic lipid is DOTAP.

15. The method of claim 1 , wherein the non-ionic triggering agent is TPGS.

16. The method of claim 1 , wherein the liposome comprises 40-80 mole % DSPC, 5-50 mole % cholesterol, 0-30 mole % DSPG, and 0-10 mole % DSPE-PEG(2000).

17. The method of claim 1 , wherein the lipid nanoparticle is a second liposome comprising 40-70 mole % DPPC, 5-20 mole % cholesterol, 0-20 mole % DOTAP, and 20-40 mole % TPGS.

18. The method of claim 1 , wherein the therapeutic agent is selected from cisplatin, oxaliplatin, carboplatin, gemcitabine, 5-fluorouracil, doxorubicin, and a taxane.

19. The method of claim 18 , wherein the therapeutic agent is selected from the group consisting of cisplatin and oxaliplatin.

20. The method of claim 1 , wherein the first liposome and the lipid nanoparticle are delivered by intraperitoneal injection.

21. The method of claim 1 , wherein the subject is human.

22. The method of claim 1 , wherein the lipid nanoparticle is administered to the subject after administration of the liposome.

23. The method of claim 22 , wherein the lipid nanoparticle is administered to the subject after the liposome has accumulated at a target site within the subject.

24. A kit for delivering a therapeutic agent to a subject, the kit comprising:
a) a first composition comprising a liposome containing a therapeutic agent; and
b) a second composition comprising a lipid nanoparticle containing a non-ionic triggering agent;

wherein the first and second compositions are stored separately prior to administration to the subject.

25. The method of claim 1 , wherein release of the therapeutic agent from the liposome following administration of the lipid nanoparticle is increased at least 3-fold, 10-fold, or 25-fold, relative to the release of the therapeutic agent from the liposome without administration of the lipid nanoparticle.

Assignees

• Mallinckrodt Llc

Inventors

• Yang Jun
• Wu Stephen H
• Herman Cliff J

Classifications

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/282

  Platinum compounds · CPC title

• A61K31/7068

  having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid · CPC title

• A61K9/127

  Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant · CPC title