Therapeutic liposome and method of treating a subject having cancer

Patent metadata

Field	Value
Publication number	US-9655847-B1
Application number	US-201615212389-A
Country	US
Kind code	B1
Filing date	Jul 18, 2016
Priority date	Jul 18, 2016
Publication date	May 23, 2017
Grant date	May 23, 2017

Abstract

A therapeutic liposome including a bilayer comprising at least one poly-unsaturated fatty acid (omega-3 fatty acid, omega-6 fatty acid, and omega-9 fatty acid), a beta-glucan, a cholesterol, and a doxorubicin. The liposome has a diameter of 100 nm to 1.5 μm. The beta-glucan and the doxorubicin are encapsulated in the liposome and the cholesterol is integral to the bilayer of the liposome.

First claim

The invention claimed is:

1. A therapeutic liposome comprising:
a bilayer enclosing an internal compartment, wherein the bilayer comprises:
all-cis-9,12,15-octadecatrienoic acid; and
a phospholipid having at least one fatty acid chain of carbon chain length C 12 to C 24 , wherein the all-cis-9,12,15-octadecatrienoic acid is not attached to the phospholipid, and the phospholipid comprises a head group selected from the group consisting of a choline, an ethanolamine, a serine, an inositol, a PEG molecule, a cell-penetrating peptide, and an antibody in reacted form;

a beta-glucan derived from oat, wherein the beta-glucan is encapsulated within the internal compartment;
cholesterol, which is integral to the bilayer; and
doxorubicin, which is encapsulated within the internal compartment;
wherein the therapeutic liposome has a diameter in a range of 130 nm to 1.5 μm.

2. The therapeutic liposome of claim 1 , wherein the phospholipid has the PEG molecule head group, and the PEG is PEG 3500 up to PEG 6000.

3. The therapeutic liposome of claim 1 , wherein the phospholipid comprises at least one poly-unsaturated fatty acid selected from the group consisting of an omega-3 fatty acid, an omega-6 fatty acid, and an omega-9 fatty acid.

4. The therapeutic liposome of claim 1 , wherein the bilayer further comprises a pH sensitive lipid.

5. The therapeutic liposome of claim 1 , wherein the beta-glucan is a linear or a branched (1,3) beta glucan, or a linear or a branched (1,3)(1,4)beta-glucan, or a combination thereof.

6. The therapeutic liposome of claim 1 , further comprising a second active agent which is an anthracycline selected from the group consisting of epirubicin, daunorubicin, idarubicin, valrubicin, and mitoxantrone, wherein the second active agent is encapsulated within the internal compartment.

7. A method of treating a cancer in a subject in need thereof, the method comprising:
administering an effective amount of a therapeutic liposome to the subject, wherein the therapeutic liposome comprises:
a bilayer enclosing an internal compartment, wherein the bilayer comprises:
all-cis-9,12,15-octadecatrienoic acid; and
a phospholipid having at least one fatty acid chain of carbon chain length C 12 to C 24 , wherein the all-cis-9,12,15-octadecatrienoic acid is not attached to the phospholipid, and the phospholipid comprises:
a head group selected from the group consisting of a choline, an ethanolamine, a serine, an inositol, a PEG molecule, a cell-penetrating peptide, and an antibody, and
a tail group comprising at least one poly-unsaturated fatty acid;

a beta-glucan, wherein the beta-glucan is derived from oat;
cholesterol, which is integral to the bilayer; and
doxorubicin, which is encapsulated within the internal compartment;
wherein the therapeutic liposome has a diameter in a range of 130 nm to 1.5 μm.

8. The method of claim 7 , wherein the therapeutic liposome further comprises a second active agent which is an anthracycline selected from the group consisting of epirubicin, daunorubicin, idarubicin, valrubicin, and mitoxantrone, wherein the second active agent is encapsulated within the internal compartment.

9. The method of claim 7 , wherein the beta-glucan is a linear or a branched (1,3) beta glucan, or a linear or a branched (1,3)(1,4)beta-glucan, or a combination thereof.

10. The method of claim 7 , wherein the therapeutic liposome is administered to the subject every 10-30 days.

11. The method of claim 7 , wherein the therapeutic liposome is administered at a rate of 0.2 mg/min-2 mg/min.

12. The method of claim 10 , wherein a cumulative dose does not exceed 400-600 mg/m 2 .

13. The method of claim 7 , wherein the cancer is at least one selected from the group consisting of an ovarian cancer, a multiple myeloma, a sarcoma, a colorectal cancer, and a breast cancer.

Assignees

• Nat Guard Health Affairs
• King Saud Bin Abdulaziz Univ For Health Sciences
• King Abdullah Int Medical Res Center

Inventors

• Halwani Majed Abdulaziz Saleh
• Alhariri Moayad Abdulaziz

Classifications

• A61K31/704

  attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)} · CPC title

• Y10S977/906

  Drug delivery · CPC title

• A61K9/127 Primary

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

• Y10S977/907

  Liposome · CPC title