Synergistic liposomal formulation for the treatment of cancer

Patent metadata

Field	Value
Publication number	US-10426728-B2
Application number	US-201415023107-A
Country	US
Kind code	B2
Filing date	Sep 18, 2014
Priority date	Sep 19, 2013
Publication date	Oct 1, 2019
Grant date	Oct 1, 2019

Abstract

The present disclosure relates to the synergistic liposomal formulation comprising, phophatidylcholine, stearylamine and anticancer drugs for the treatment of cancer. The PC:SA cationic liposome encapsulated camptothecin (CPT) and doxorubicin (DOX) formulations show enhanced synergistic anti-cancer effect and provide improved therapeutic index as compared to either the liposome or drug alone. The present disclosure also relates to the use of Cationic liposomal preparation of phosphatidylcholine:stearylamine (PC:SA) showing anticancer effect. The SA-bearing liposome and drug entrapped in the liposome are effective against cancer both in vitro and in vivo, without causing any adverse effect on host.

First claim

We claim:

1. A synergistic liposomal formulation for the treatment of cancer, wherein said synergistic liposomal formulation consists of drug-free phosphatidylcholine (PC) and stearylamine (SA) liposomes, and camptothecin (CPT), doxorubicin (DOX), or combinations thereof, and wherein phosphatidylcholine, stearylamine, and camptothecin w/w molar ratio in said synergistic liposomal formulation is 7(PC):2(SA):0.7(CPT) or wherein phosphatidylcholine, stearylamine, and doxorubicin w/w molar ratio in said synergistic liposomal formulation is 7(PC):2(SA):0.5(DOX).

2. The synergistic liposomal formulation as claimed in claim 1 , wherein, said synergistic liposomal formulation is prepared in a form selected from the group consisting of dehydration-rehydration vesicles (DRV), reverse phase evaporation vesicle (REV), and multilamellar vesicles (MLV).

3. The synergistic liposomal formulation as claimed in claim 1 , wherein said synergistic liposomal formulation is used for the treatment of murine melanoma, rat glioma, colorectal adenocarcinoma, human colon carcinoma, chronic myelogenous leukemia, acute lymphoblastic leukemia, and ascites carcinoma in vitro.

4. The synergistic liposomal formulation as claimed in claim 1 , wherein the dose of said synergistic liposomal formulation is used at 20-140 μg/ml with respect to PC.

5. A drug-free liposomal formulation for use in the treatment of cancer, wherein said liposomal formulation comprises of phosphatidylcholine (PC) and stearylamine (SA) in a molar ratio of 7:2.

6. The liposomal formulation as claimed in claim 5 , wherein EC50 value of said liposomal formulation against cancer cell lines is in the range of 60-80 μg/ml.

7. The liposomal formulation as claimed in claim 5 , wherein said liposomal formulation for intravenous administration is 800 mg/Kg body weight.

8. The liposomal formulation as claimed in claim 5 , wherein said liposomal formulation for intravenous or intra-peritoneal administration is 1.7 g/Kg body weight.

9. The liposomal formulation as claimed in claim 5 , said liposomal formulation for subcutaneous administration is 7 mg/Kg body weight with respect to PC.

10. The synergistic liposomal formulation as claimed in claim 1 , wherein for subcutaneous administration the anti-cancer drug CPT is administered at 350 μg/Kg body weight entrapped in 7 mg/Kg body weight of PC-SA.

11. A synergistic formulation consisting of camptothecin (CPT), doxorubicin (DOX), or combinations thereof, and liposomes consisting of phosphatidylcholine (PC) and stearylamine (SA), wherein phosphatidylcholine, stearylamine, and camptothecin w/w molar ratio in said synergistic formulation is 7(PC):2(SA):0.7(CPT) or wherein phosphatidylcholine, stearylamine, and doxorubicin w/w molar ratio in said synergistic formulation is 7(PC):2(SA):0.5(DOX).

12. The liposomal formulation as claimed in claim 5 which consists of phosphatidylcholine (PC) and stearylamine (SA).

Assignees

• Council Scient Ind Res

Inventors

• Ali Nahid
• De Manjarika
• Sen Triparna

Classifications

• A61K31/542

  ortho- or peri-condensed with heterocyclic ring systems · 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

• A61K47/24

  containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids · CPC title

• A61K47/18

  Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids · 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