Liposomal curcumin for treatment of cancer

Patent metadata

Field	Value
Publication number	US-9283185-B2
Application number	US-201113117807-A
Country	US
Kind code	B2
Filing date	May 27, 2011
Priority date	Mar 7, 2003
Publication date	Mar 15, 2016
Grant date	Mar 15, 2016

Abstract

The present invention provides a compositions and methods for the treatment of cancer, including pancreatic cancer, breast cancer and melanoma, in a human patient. The methods and compositions of the present invention employ curcumin or a curcumin analogue encapsulated in a colloidal drug delivery system, preferably a liposomal drug delivery system. Suitable colloidal drug delivery systems also include nanoparticles, nanocapsules, microparticles or block copolymer micelles. The colloidal drug delivery system encapsulating curcumin or a curcumin analogue is administered parenterally in a pharmaceutically acceptable carrier.

First claim

What is claimed is:

1. A method for treating melanoma, pancreatic and breast carcinoma cells in a mammalian subject, comprising:
a) formulating a PEG containing stealth liposome encapsulating at least one of a curcumin or a curcumin analogue in an amount sufficient to treat a pancreatic cancer, breast cancer or a melanoma; and
b) administering the PEG containing stealth liposome to a mammalian subject in a pharmaceutically acceptable carrier, wherein the encapsulated curcumin or curcumin analogue have a reduced toxicity, wherein the liposome comprises a lipid formulation selected from: DMPC; DMPC:Chol 9:1; DMPC:DMPG 9:1; DMPC:Chol:DMPG 8:1:1; DPPC:DMPG 9:1; DPPC:Chol:DMPG 8:1:1; DMPC:DMPE-PEG-2000 95:5; DMPC:Chol:DMPE-PEG-2000 90:10:05; DMPC:DSPE-PEG-2000 95:5; DMPC:Chol:DSPE-PEG-2000 90:10:05; DMPC/DMPG 7:3; DPPC/DMPG 7:3; DPPC/DMPG 9:1; or DOPC [10:1].

2. The method of claim 1 , wherein the mammalian subject is a human cancer patient.

3. The method of claim 1 , wherein the PEG containing stealth liposome comprises nanocapsules.

4. The method of claim 1 , wherein the PEG containing stealth liposome encapsulates a curcumin analogue selected from the group consisting of Ar-tumerone, methylcurcumin, demethoxy curcumin, bisdemethoxycurcumin, sodium curcuminate, dibenzoylmethane, acetylcurcumin, feruloyl methane, tetrahydrocurcumin, 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (curcumin1), 1,7-bis(piperonyl)-1,6-heptadiene-3,5-dione (piperonyl curcumin) 1,7-bis(2-hydroxy naphthyl)-1,6-heptadiene-2,5-dione (2-hydroxyl naphthyl curcumin) and 1,1-bis(phenyl)-1,3,8,10 undecatetraene-5,7-dione.

5. A composition for treating melanoma, pancreatic and breast carcinoma cells in a patient or other mammalian subject comprising curcumin or a curcumin analogue in an amount sufficient to treat the pancreatic cancer, a breast cancer or the melanoma, wherein the curcumin or curcumin analogue is encapsulated in a PEG containing stealth liposome drug delivery system, wherein the encapsulated curcumin or curcumin analogue have a reduced toxicity, and wherein the liposome comprises a lipid formulation selected from: DMPC; DMPC:Chol 9:1; DMPC:DMPG 9:1; DMPC:Chol:DMPG 8:1:1; DPPC:DMPG 9:1; DPPC:Chol:DMPG 8:1:1; DMPC:DMPE-PEG-2000 95:5; DMPC:Chol:DMPE-PEG-2000 90:10:05; DMPC:DSPE-PEG-2000 95:5; DMPC:Chol:DSPE-PEG-2000 90:10:05; DMPC/DMPG 7:3; DPPC/DMPG 7:3; DPPC/DMPG 9:1; or DOPC [10:1].

6. The composition of claim 5 , wherein the a PEG containing stealth liposome drug delivery system encapsulating curcumin or a curcumin analogue is in suspension in a pharmaceutically acceptable carrier.

7. The composition of claim 5 , wherein the a PEG containing stealth liposome drug delivery system encapsulating curcumin or a curcumin analogue is a lyophilized powder.

8. The composition of claim 5 , wherein the a PEG containing stealth liposome drug delivery system encapsulates a curcumin analogue selected from the group consisting of Ar-tumerone, methylcurcumin, demethoxy curcumin, bisdemethoxycurcumin, sodium curcuminate, dibenzoylmethane, acetylcurcumin, feruloyl methane, tetrahydrocurcumin, 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (curcumin1), 1,7-bis(piperonyl)-1,6-heptadiene-3,5-dione (piperonyl curcumin) 1,7-bis(2-hydroxy naphthyl)-1,6-heptadiene-2,5-dione (2-hydroxyl naphthyl curcumin) and 1,1-bis(phenyl)-1,3,8,10 undecatetraene-5 ,7-dione.

Assignees

• Kurzrock Razelle
• Li Lan
• Mehta Kapil
• Aggarwal Bharat Bhushan
• Univ Texas

Inventors

• Kurzrock Razelle
• Li Lan
• Mehta Kapil
• Aggarwal Bharat Bhushan

Classifications

• A61K31/12 Primary

  Ketones · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K9/127

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

• A61K9/1272 Primary

  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}) · CPC title

• A61P35/00

  Antineoplastic agents · CPC title