Sustained-release compositions comprising a therapeutic agent for treating depression or anxiety and uses thereof

1. A pharmaceutical composition, comprising

(a) at least one liposome comprising a bilayer membrane, said bilayer membrane comprises a first lipid that is HSPC, DMPC or any combination thereof, cholesterol and a second lipid that is PEG-DSPE;

(b) a trapping agent that is triethylammonium sucrose octasulfate, ammonium sulfate, or any combination thereof; and

(c) a therapeutic agent that is ketamine,

wherein the molar ratio of the therapeutic agent to the lipid is equal to or higher than about 0.2, the therapeutic agent is encapsulated in the liposomes with an encapsulation efficiency higher than about 60% and the mean particle size of the liposome is from about 50 nm to about 20 μm.

2. The pharmaceutical composition of claim 1 , wherein the mole % of first lipid: second lipid: cholesterol is 40-70%: 0.1-25%: 25-45%.

3. The pharmaceutical composition of claim 1 , wherein the concentration of triethylammonium sucrose octasulfate is about 10 to 200 mM.

4. The pharmaceutical composition of claim 1 , wherein the concentration of ammonium sulfate is about 100 to 600 mM.

5. The pharmaceutical composition of claim 1 , wherein the bilayer membrane comprises a first lipid that is HSPC, cholesterol and a second lipid that is PEG-DSPE, with an encapsulation efficiency higher than about 75%.

6. The pharmaceutical composition of claim 1 , wherein said ketamine is selected from the group consisting essentially of (R,S)-ketamine, (R)-ketamine and (S)-ketamine.

7. The pharmaceutical composition of claim 1 , further comprising a pharmaceutically acceptable excipient, a diluent, a medium for an active ingredient, a preservative, a cryoprotectant or a combination thereof.

8. A method of treating depression or anxiety, comprising:

administering the pharmaceutical composition of claim 1 to a subject in need thereof.

9. The method of claim 8 , wherein the half-life of the therapeutic agent in the pharmaceutical composition is extended by at least 2-fold compared to that of a free therapeutic agent.

10. The method of claim 8 , wherein the pharmaceutical composition is administered at least once every three days, at least once every week, at least once every two weeks or at least once a month.

11. The method of claim 8 , wherein the pharmaceutical composition is administered by cutaneous injection.

12. The method of claim 11 , wherein the cutaneous injection includes subcutaneous, subdermal, intradermal or intramuscular route.

13. A pharmaceutical composition, comprising

(a) at least one liposome comprising a bilayer membrane, said bilayer membrane comprises a first lipid that is HSPC, DPPC or any combination thereof, cholesterol and optionally a second lipid that is PEG-DSPE, DPPG or any combination thereof;

(b) a trapping agent that is 10 to 200 mM triethylammonium sucrose octasulfate, 300 to 600 mM ammonium sulfate, 100 to 600 mM ammonium phosphate or any combination thereof; and

(c) a therapeutic agent that is scopolamine,

wherein the molar ratio of the therapeutic agent to the lipid is equal to or higher than about 0.15, the therapeutic agent is encapsulated in the liposomes with an encapsulation efficiency higher than about 60% and the mean particle size of the liposome is from about 50 nm to about 20 μm.

14. The pharmaceutical composition of claim 13 , wherein the mole % of first lipid: second lipid: cholesterol is 40-70%: 0.1-25%: 25-45%.

15. The pharmaceutical composition of claim 13 , wherein the trapping agent is 10 to 200 mM triethylammonium sucrose octasulfate, 300 to 600 mM ammonium sulfate, or any combination thereof; the molar ratio of the therapeutic agent to the lipid is equal to or higher than about 0.15, the therapeutic agent is encapsulated in the liposomes with an encapsulation efficiency higher than about 65%.

16. The pharmaceutical composition of claim 13 , further comprising a pharmaceutically acceptable excipient, a diluent, a medium for an active ingredient, a preservative, a cryoprotectant or a combination thereof.

17. A method of treating depression or anxiety, comprising:

administering the pharmaceutical composition of claim 13 to a subject in need thereof.

18. The method of claim 17 , wherein the half-life of the therapeutic agent in the pharmaceutical composition is extended by at least 2-fold compared to that of a free therapeutic agent.

19. The method of claim 17 , wherein the pharmaceutical composition is administered at least once every three days, at least once every week, at least once every two weeks or at least once a month.

20. The method of claim 17 , wherein the pharmaceutical composition is administered by cutaneous injection.