Delivery of hydrophobic active agent particles
Embodiments of the invention include drug delivery coatings and devices including the same. In an embodiment, the invention includes a drug delivery coating including a polymeric layer. The polymeric layer can include a hydrophilic outer surface. The coating can also include a matrix contacting the hydrophilic outer surface. The matrix can include a particulate hydrophobic therapeutic agent and a cationic agent. The polymeric layer can further include a hydrophilic polymer having pendent photoreactive groups and a photo-crosslinker including two aryl ketone functionalities. Other embodiments are also included herein.
1. A medical device comprising
a catheter shaft;
a balloon disposed around the catheter shaft, the balloon comprising an underlying polymeric layer, the polymeric layer comprising an outer surface;
a positively charged hydrophilic polymeric layer disposed on the outer surface of the underlying polymeric layer;
a matrix disposed on the positively charged hydrophilic polymeric layer, the matrix comprising
a particulate hydrophobic therapeutic agent; and
a cationic agent selected from the group consisting of cationic lipids, neutral lipids with cationic groups, and cationic polymers;
wherein the particulate hydrophobic agent coexists in the matrix with the cationic agent.
2. The medical device of claim 1 , the particulate hydrophobic therapeutic agent having an average diameter of between 100 nm and 10 μm.
3. The medical device of claim 1 , the cationic agent having a molecular weight of between 2.5 kDa and 2,000 kDa.
4. The medical device of claim 1 , the cationic agent having a molecular weight of between 50 kDa and 100 kDa.
5. The medical device of claim 1 , the particulate hydrophobic therapeutic agent and the cationic agent forming coated therapeutic agent particles.
6. The medical device of claim 1 , the cationic agent selected from the group consisting of polyethyleneimine and DOTAP.
7. A device for delivering a therapeutic agent to a vessel wall comprising:
a polymeric balloon disposed on a catheter, the polymeric balloon comprising an underlying polymeric layer comprising an outer surface;
a positively charged hydrophilic polymeric layer disposed on the outer surface of the underlying polymeric layer; and
a therapeutic agent composition disposed on the positively charged hydrophilic polymeric layer, the therapeutic agent composition consisting essentially of an antiproliferative agent and a cationic polymer, wherein the cationic polymer is selected from the group consisting of a polyamine, a polyimine, a cationic polypeptide, or combinations thereof.
8. The device of claim 7 , the antiproliferative agent selected from paclitaxel and sirolimus (rapamycin).
9. The device of claim 7 , the cationic polymer comprising polyethyleneimine.
10. The device of claim 7 , the polypeptide comprising at least one of poly-L-lysine, poly-L-ornithine, and poly(4-hydroxy-L-proline ester).
11. The device of claim 7 , wherein the percent ratio of cationic polymer to antiproliferative agent is from about 97/3 to about 88/12 wt./wt.
12. The device of claim 7 , wherein inflation of the polymeric balloon after insertion of the device into a vessel causes the therapeutic agent composition to contact a wall of the vessel and be transferred thereto.
13. The device of claim 12 , wherein contact with the wall of the vessel causes at least some of the therapeutic agent to be transferred to the wall of the vessel within 30 seconds.
14. A method of forming a device for delivering a therapeutic agent to a vessel wall comprising:
providing a polymeric balloon disposed on a catheter, the polymeric balloon comprising an underlying polymeric layer comprising an outer surface;
disposing a positively charged hydrophilic polymeric layer disposed onto the outer surface of the underlying polymeric layer; and
disposing a therapeutic agent composition onto the positively charged hydrophilic polymeric layer; the therapeutic agent composition consisting essentially of an antiproliferative agent and a cationic polymer, wherein the cationic polymer is selected from the group consisting of a polyamine, a polyimine, a cationic polypeptide, or combinations thereof.
15. The method of claim 14 , the antiproliferative agent selected from paclitaxel and sirolimus (rapamycin).
16. The method of claim 14 , the cationic polymer comprising polyethyleneimine.
17. The method of claim 14 , the polypeptide comprising at least one of poly-L-lysine, poly-L-ornithine, and poly(4-hydroxy-L-proline ester).
18. The method of claim 14 , wherein the percent ratio of cationic polymer to antiproliferative agent is from about 97/3 to about 88/12 wt./wt.
19. The method of claim 14 , wherein inflation of the polymeric balloon after insertion of the device into a vessel causes the therapeutic agent composition to contact a wall of the vessel and be transferred thereto.
20. The method of claim 14 , wherein contact with the wall of the vessel causes at least some of the therapeutic agent to be transferred to the wall of the vessel within 30 seconds.