Delivery of coated hydrophobic active agent particles
View Patent ↗Embodiments of the invention include devices and coatings for devices including coated hydrophobic active agent particles. In an embodiment, the invention includes a drug delivery device including a substrate; and coated therapeutic agent particles disposed on the substrate, the coated therapeutic agent particles comprising a particulate hydrophobic therapeutic agent; and a cationic agent in contact with the particulate hydrophobic therapeutic agent. Other embodiments are also included herein.
1. A drug delivery device comprising:
a substrate;
a hydrophilic polymer layer disposed on the surface of the substrate; and
an active agent layer consisting of coated therapeutic agent particles disposed on the surface of the hydrophilic polymer layer to form the outside surface of the drug delivery device, wherein the coated therapeutic agent particles are comprised of:
a particulate hydrophobic therapeutic agent core, the particulate hydrophobic therapeutic agent core having an average diameter of between 100 nm and 10 μm; and
a cationic agent coating disposed on the surface of the particulate hydrophobic therapeutic agent core and configured to be in direct contact with a lipid bilayer of a cell membrane.
2. The drug delivery device of claim 1 , the particulate hydrophobic therapeutic agent core having an average diameter of between 0.3 μm to about 1 μm.
3. The drug delivery device of claim 1 , the cationic agent coating having a molecular weight of between 2.5 kDa and 2,000 kDa.
4. The drug delivery device of claim 1 , the cationic agent coating having a molecular weight of between 50 kDa and 100 kDa.
5. The drug delivery device of claim 1 , the coated therapeutic agent particles exhibiting a Zeta potential of greater than +10 mV.
6. The drug delivery device of claim 1 , further comprising nucleic acids associated with the cationic agent coating.
7. The drug delivery device of claim 1 , the particulate hydrophobic therapeutic agent core having a solubility in water at 25 degrees Celsius of less than 100 μg/mL.
8. The drug delivery device of claim 1 , the cationic agent coating selected from the group consisting of cationic lipids, cationic polymers, and lipidoids.
9. The drug delivery device of claim 1 , the cationic agent coating comprising polyethyleneimine (PEI).
10. The drug delivery device of claim 1 , the cationic agent coating comprising 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or polyamidoamine dendrimers (PAMAM).
11. The drug delivery device of claim 1 , the particulate hydrophobic therapeutic agent core selected from the group consisting of paclitaxel, sirolimus, zotarolimus, everolimus, temsirolimus, pimecrolimus, tacrolimus, ridaforolimus and analogs thereof.
12. The drug delivery device of claim 1 , the hydrophilic polymer layer comprising polyacrylamide.
13. The drug delivery device of claim 1 , the hydrophilic polymer layer comprising polyvinylpyrrolidone.
14. The drug delivery device of claim 1 , the hydrophilic polymer layer covalently bonded to the substrate.
15. The drug delivery device of claim 1 , the hydrophilic polymer layer cross-linked with a photoactivatable cross-linking agent.
16. The drug delivery device of claim 1 , the device comprising a drug-containing balloon catheter.
17. A drug delivery coating comprising:
a polymeric layer, the polymeric layer comprising a hydrophilic surface; and
an outermost surface layer formed of an active agent layer disposed on the surface of the polymeric layer, the active agent layer consisting of coated therapeutic agent particles, the coated therapeutic agent particles comprising
a particulate hydrophobic therapeutic agent core, the particulate hydrophobic therapeutic agent core having an average diameter of between 100 nm and 10 μm; and
a cationic agent coating disposed on the surface of the particulate hydrophobic therapeutic agent core and configured to be in direct contact with a lipid bilayer of a cell membrane.
18. The drug delivery coating of claim 17 , the particulate hydrophobic therapeutic agent core having an average diameter of between 0.3 μm to about 1 μm.
19. The drug delivery coating of claim 17 , the cationic agent coating having a molecular weight of between 2.5 kDa and 2,000 kDa.
20. The drug delivery coating of claim 17 , the cationic agent coating having a molecular weight of between 50 kDa and 100 kDa.