Composition and method for delivery of hydrophobic active agents
View Patent ↗Disclosed herein is a delivery composition for administering a hydrophobic active agent. In one embodiment, a delivery composition for local administration of a hydrophobic active agent to a tissue or organ of a patient is disclosed. In one embodiment, the delivery composition includes a cationic delivery agent, a therapeutically effective amount of a hydrophobic active agent and a pharmaceutically acceptable aqueous carrier. In one embodiment, the cationic delivery agent includes polyethyleneimine (PEI). In a more specific embodiment, the cationic delivery agent includes branched PEI. Methods of making the delivery composition, as well as kits and methods of use are also disclosed.
1. A delivery composition for local administration of a hydrophobic active agent, the delivery composition comprising:
a cationic delivery agent comprising an agent selected from the group consisting of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), polyamidoamine dendrimers (PAMAM), polypropylenimine, and polyethyleneimine (PEI) homopolymer;
the hydrophobic active agent, wherein the hydrophobic active agent interfaces with the cationic delivery agent; and
a pharmaceutically acceptable aqueous carrier;
the cationic delivery agent effective to improve adhesion of the hydrophobic active agent to surfaces;
wherein the delivery composition is in the form of a liquid immediately prior to local administration.
2. The composition according to claim 1 , wherein the cationic delivery agent comprises branched PEI.
3. The composition according to claim 2 , wherein the branched PEI has a molecular weight of at least about 25 kD and up to about 5000 kD.
4. The composition according to claim 2 , wherein the branched PEI has a molecular weight of at least about 100 kD and up to about 3000 kD.
5. The composition according to claim 2 , wherein branched PEI has a ratio of primary:secondary:tertiary amines between about 1:3:1 and about 1:1:1.
6. The composition according to claim 2 , wherein branched PEI has a ratio of primary:secondary:tertiary amines of between about 1:2:1 and about 1:1:1.
7. The composition according to claim 1 , comprising cationic delivery agent:hydrophobic active agent at a ratio of at least about 1:1 and up to about 1:25.
8. The composition according to claim 1 , comprising cationic delivery agent:hydrophobic active agent at a ratio of at least about 1:2 and up to about 1:20.
9. The composition according to claim 1 , comprising cationic delivery agent:hydrophobic active agent at a ratio of at least about 1:5 and up to about 1:10.
10. The composition according to claim 1 , comprising at least about 1 mg/ml and up to about 25 mg/ml cationic delivery agent.
11. The composition according to claim 1 , comprising at least about 5 mg/ml and up to about 125 mg/ml hydrophobic active agent.
12. The composition according to claim 1 , wherein the aqueous carrier is selected from water and buffered saline.
13. The composition according to claim 1 , comprising a pH between 5 and 9.
14. The composition according to claim 1 , wherein the hydrophobic active agent is selected from an antiproliferative, analgesic, anti-inflammatory, anti-arrhythmic, anti-bacterial, anti-coagulant, anti-hypertensive, anti-muscarinic, anti-neoplastic, beta-blocker, cardiac inotropic agent, corticosteroids, lipid regulating agents, anti-anginal agents, and combinations thereof.
15. The composition according to claim 1 , wherein the hydrophobic active agent comprises an antiproliferative selected from paclitaxel, sirolimus, everolimus, biolimus A9, zotarolimus, tacrolimus, and pimecrolimus and mixtures thereof.
16. A method for local administration of a hydrophobic active agent to a tissue or organ of a patient, the method comprising:
preparing a composition comprising
a cationic delivery agent comprising an agent selected from the group consisting of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), polyamidoamine dendrimers (PAMAM), polypropylenimine, and polyethyleneimine (PEI) homopolymer;
the hydrophobic active agent, wherein the hydrophobic active agent interfaces with the cationic delivery agent; and
a pharmaceutically acceptable aqueous carrier, the cationic delivery agent effective to improve adhesion of the hydrophobic active agent to surfaces; and
applying the composition to the tissue or organ of the patient, wherein the composition is in a liquid form as applied.
17. The method of claim 16 , wherein the PEI has a molecular weight of at least about 25 kD and up to about 5000 kD.