Synergistic liposomal formulation for the treatment of cancer

Patent metadata

Field	Value
Publication number	US-2016228366-A1
Application number	US-201415023107-A
Country	US
Kind code	A1
Filing date	Sep 18, 2014
Priority date	Sep 19, 2013
Publication date	Aug 11, 2016
Grant date	—

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

I/we claim:

1 . A synergistic liposomal formulation for the treatment of cancer wherein the formulation comprises, phophatidylcholine, stearylamine and anticancer drugs.

2 . The liposomal formulation as claimed in claim 1 , wherein the anticancer drugs are selected from the group consisting of camptothecin (CPT), doxorubicin (DOX), cisplatin, and paclitaxel.

3 . The synergistic liposomal formulation as claimed in claim 1 , wherein the ratio of phatidylcholine, stearylamine and camptothecin is 7(PC):2(SA):0.7(CPT).

4 . The synergistic liposomal formulation as claimed in claim 1 , wherein the ratio of phatidylcholine, stearylamine and doxorubicin is 7(PC):2(SA):0.5(DOX).

5 . The liposomal formulation as claimed in claim 1 wherein, the formulation is prepared in the form of dehydration-rehydration vesicles (DRV), reverse phase evaporation vesicle (REV) and multilamellar vesicles (MLV).

6 . The liposomal formulation as claimed in claim 1 , wherein the 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.

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

8 . Use of liposomal formulation for the treatment of cancer, wherein the said formulation comprises of phosphatidylcholine (PC) and stearylamine (SA) in a molar ratio of 7:2.

9 . The use of liposomal formulation as claimed in claim 8 wherein EC50 value of liposomal formulation against cancer cell lines is in the range of 60-80 μg/ml.

10 . The use of liposomal formulation as claimed in claim 8 , wherein the dosage of the said formulation is administered at 3 doses of 800 mg/Kg body weight (intravenously) with respect to PC against DEN induced hepatocarcinoma in rats.

11 . A liposomal formulation as claimed in claim 8 , wherein the dosage of the said formulation is administered at a single shot injection of 1.7 g/Kg body weight with respect to PC (intravenously and intra-peritoneally) in Swiss albino mice to inhibit growth of Ehrlichs ascites carcinoma (EAC).

12 . The use of liposomal formulation as claimed in claim 8 , wherein the dosage of the said formulation is administered at a single dose of 7 mg/Kg body weight (subcutaneously) with respect to PC against B16F10 melanoma in vivo.

13 . A liposomal formulation as claimed in claim 3 , wherein the anti-cancer drug CPT is administered at a single dose of 350 μg/Kg body weight entrapped in 7 mg/Kg body weight of the said formulation with respect to PC (subcutaneously) for increased anti-tumor effect of the free liposome against B16F10 melanoma in vivo.

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

• A61K31/704

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

• A61K47/24

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

• 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