COMPOSITIONS OF POLYUNSATURATED FATTY ACIDS AND METHODS OF USE THEREOF
Pharmaceutical compositions with selective tumoricial activity comprising polyunsaturated fatty acids or a pharmaceutically acceptable salt or derivative thereof, in an aqueous solution or emulsion are provided. Methods associated with preparation and use of such compositions and methods to selectively cause tumoricial and/or anti-angiogenic action in a neoplastic region, such as cancer, are also provided.
1 . A pharmaceutical composition comprising:
a polyunsaturated fatty acid in the free acid form;
saline or phosphate buffered saline; and
from 0.01% to 0.0001% ethanol.
2 . The pharmaceutical composition of claim 1 , wherein the polyunsaturated fat is linoleic acid, gamma-linolenic acid, di-homo gamma linolenic acid, arachidonic acid, alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, conjugated linoleic acid, or combinations thereof.
3 . The pharmaceutical composition of claim 1 , wherein the polyunsaturated fatty acid is gamma-linolenic acid.
4 . The pharmaceutical composition of claim 1 , wherein the polyunsaturated fatty acid is conjugated to a tumor necrosis factor a, an interferon, an anti-neoplastic agent, an antibody, an anti-cancer agent or combinations thereof
5 . The pharmaceutical composition of claim 4 , wherein the anti-cancer agent is vincristine, adriamycin, doxorubicin, cyclophosphamide, cis-platinum, L-asparaginase, procarbazine, camptothecin, taxol, 5-fluorouracil, busulfan, or combinations thereof.
6 . The pharmaceutical composition of claim 1 , further comprising a tumor necrosis factor a, an interferon, an anti-neoplastic agent, an antibody, an anti-cancer agent or combinations thereof.
7 . The pharmaceutical composition of claim 6 , wherein the anti-cancer agent is vincristine, adriamycin, doxorubicin, cyclophosphamide, cis-platinum, L-asparaginase, procarbazine, camptothecin, taxol, 5-fluorouracil, busulfan, or combinations thereof.
8 . The pharmaceutical composition of claim 4 , wherein molar ratio of polyunsaturated fatty acid to tumor necrosis factor a or interferon ranges from 2:1 to 1:3.
9 . The pharmaceutical composition of claim 1 , wherein the concentration of polyunsaturated fatty acid ranges from 5 to 75%.
10 . The pharmaceutical composition of claim 9 , wherein the concentration of polyunsaturated fatty acid ranges from 25 to 75%.
11 . The pharmaceutical composition of claim 1 , further comprising a stabilizing agent.
12 . The pharmaceutical composition of claim 11 , wherein the stabilizing agent comprises lithium.
13 . A method for treatment of cancer comprising:
identifying a neoplastic region in a subject in need thereof;
administering a therapeutically effective amount of the pharmaceutical composition of claim 1 to the neoplastic region.
14 . The method of claim 13 , wherein administering comprises administering the pharmaceutical composition intratumorally.
15 . The method of claim 13 , wherein administering comprises administering the pharmaceutical composition via a catheter placed in a tumor bed.
16 . The method of claim 13 , comprising administering the pharmaceutical composition daily.
17 . The method of claim 13 , wherein the neoplastic region comprises glioma.
18 . The method of claim 13 , wherein the composition is steadily and predictably administered in therapeutically effective amounts over 1-10 days.
19 . The method of claim 13 , wherein the pharmaceutical composition comprises gamma-linolenic acid.
20 . A method for preparing a pharmaceutical composition of claim 1 , the method comprising,
dissolving a polyunsaturated fatty acid in free acid form in a solution comprising ethanol to form a first mixture; and
diluting the first mixture in saline or phosphate buffered saline such that the final concentration of ethanol ranges from 0.001% to 0.01%.
21 . The method of claim 20 , wherein the polyunsaturated fatty acid is gamma-linolenic acid.
22 . The method of claim 20 , further comprising including a stabilizing agent in the first mixture or in the diluted first mixture.
23 . The method of claim 22 , wherein the stabilizing agent is lithium.