Composition and method for delivery of hydrophobic active agents
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 kit comprising:
a delivery composition in a liquid form comprising:
(A) a hydrophobic active agent; and
(B) a cationic delivery agent selected from the group consisting of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), polyamidoamine dendrimers (PAMAM), polypropylenimine, and polyethyleneimine (PEI) homopolymer;
wherein the hydrophobic active agent interfaces with the cationic delivery agent; and
wherein the cationic delivery agent is effective to improve adhesion of the hydrophobic active agent to surfaces.
2. The kit according to claim 1 , comprising solid hydrophobic active agent.
3. The kit according to claim 1 , comprising hydrophobic active agent in an aqueous solution.
4. The kit according to claim 2 , comprising amorphous hydrophobic active agent.
5. The kit according to claim 2 , comprising crystalline hydrophobic active agent.
6. The kit according to claim 1 , comprising amorphous cationic delivery agent.
7. The kit according to claim 1 , comprising crystalline cationic delivery agent.
8. The kit according to claim 1 , comprising cationic delivery agent in an aqueous solution.
9. The kit according to claim 1 , further comprising a pharmaceutically acceptable aqueous carrier.
10. The kit according to claim 1 , further comprising instructions for use.
11. The kit according to claim 1 , comprising:
a suspension comprising the hydrophobic active agent; and
instructions to combine the cationic delivery agent with the suspension of hydrophobic active agent.
12. The kit according to claim 1 , comprising:
a mixture of solid hydrophobic active agent and cationic delivery agent having a ratio of hydrophobic active agent:cationic delivery agent of less than about 1:5 and instructions to reconstitute the mixture with a pharmaceutically acceptable aqueous carrier.
13. The kit according to claim 1 , comprising:
a suspension comprising the solid hydrophobic active agent and cationic delivery agent in a pharmaceutically acceptable aqueous carrier, wherein the suspension has a pH of between about 5 and about 9.
14. The kit 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 kit according to claim 1 , wherein the hydrophobic active agent comprises an antiproliferative selected from paclitaxel, sirolimus (rapamycin), everolimus, biolimus A9, zotarolimus, tacrolimus, and pimecrolimus and mixtures thereof.