Methods and systems for inhibiting vascular inflammation
Methods and kits for delivering pharmaceutical agents to an adventitia and other regions outside an external elastic lamina (EEL) surrounding a blood vessel utilize a catheter having a needle. The needle is positioned in up to 5 mm beyond the EEL and delivers an amount of a pharmaceutical agent sufficient to circumferentially permeate around the blood vessel and, in many cases, extend longitudinally and radially along the blood vessel. Confirmation that a delivery aperture of the needle lies beyond the EEL may be required before delivering the pharmaceutical agent. In one example, catheters are used to deliver dexamethasone and other anti-inflammatory agents to a peripheral vasculature and other vasculature to treat peripheral vascular disease and other conditions.
1. A method for inhibiting inflammation in a patient's vasculature, said method comprising:
positioning a catheter within a lumen of a blood vessel of the patient, the blood vessel having had a revascularization procedure performed thereon;
advancing a needle radially outwardly from the catheter through a wall of the blood vessel and into an adventitial tissue surrounding the blood vessel; and
delivering an anti-inflammatory agent into the adventitial tissue and a perivascular tissue through the needle advanced into the adventitial tissue in an amount sufficient to inhibit inflammation of the blood vessel after the revascularization procedure, wherein the anti-inflammatory agent consists essentially of dexamethasone or dexamethasone phosphate,
wherein the inhibition or a reduction of inflammation is characterized by a detectable lack of a significant increase or a detectable reduction, respectively, in monocyte chemotractive protein-1 (MCP-1) levels in circulating blood.
2. The method of claim 1 , wherein the patient is at risk of or suffering from peripheral artery disease.
3. The method of claim 2 , wherein the blood vessel is an artery selected from the group consisting of iliac arteries, femoral arteries, and popliteal arteries.
4. The method of claim 1 , wherein the anti-inflammatory agent is delivered at a dosage of 3.2 mg to 24 mg.
5. The method of claim 1 , wherein the anti-inflammatory agent is delivered at a dosage of 0.5 to 2.7 mg per cm of lesion.
6. The method of claim 1 , wherein the anti-inflammatory agent is delivered at a dosage of 2.4 mg to 8.0 mg per infusion.
7. The method of claim 1 , wherein the delivered anti-inflammatory agent distributes completely circumferentially through the adventitial tissue surrounding the blood vessel at a delivery site.
8. The method of claim 1 , wherein the anti-inflammatory agent is delivered right after revascularization.
9. The method of claim 1 , further comprising delivering a contrast agent for visualization through the needle advanced into the adventitial tissue.
10. The method of claim 9 , wherein the anti-inflammatory agent is delivered with the contrast agent at a primary therapeutic agent to contrast agent ratio of 4:1.
11. The method of claim 1 , wherein the anti-inflammatory agent is incorporated into a lipophilic carrier or adjuvant.
12. The method of claim 1 , wherein the anti-inflammatory agent is delivered with saline.
13. The method of claim 1 , wherein the anti-inflammatory agent is incorporated into liposomes.
14. The method of claim 1 , wherein the anti-inflammatory agent is delivered with an erodable polymer.
15. The method of claim 1 , wherein the anti-inflammatory agent is delivered with a solubilizer.
16. The method of claim 1 , wherein the anti-inflammatory agent is provided as microparticles or nanoparticles.
17. The method of claim 1 , wherein the method further comprises withdrawing the needle from the adventitial tissue and withdrawing the catheter out of the blood vessel of the patient after delivering the anti-inflammatory agent.
18. A method for inhibiting inflammation in a patient's vasculature, said method comprising:
positioning a catheter within a lumen of a blood vessel of the patient, the blood vessel having had a revascularization procedure performed thereon;
advancing a needle radially outwardly from the catheter through a wall of the blood vessel and into an adventitial tissue surrounding the blood vessel; and
delivering an anti-inflammatory agent into the adventitial tissue and a perivascular tissue through the advanced needle in an amount sufficient to inhibit inflammation of the blood vessel after the revascularization procedure, wherein the anti-inflammatory agent comprises dexamethasone or dexamethasone phosphate, and wherein the dexamethasone or the dexamethasone phosphate is delivered into the adventitial tissue and the perivascular tissue at a dosage of 0.5 to 2.7 mg per cm of lesion,
wherein the inhibition or a reduction of inflammation is characterized by a detectable lack of a significant increase or a detectable reduction, respectively, in monocyte chemotractive protein-1 (MCP-1) levels in circulating blood.
19. The method of claim 18 , wherein the patient is at risk of or suffering from peripheral artery disease.
20. The method of claim 19 , wherein the blood vessel is an artery selected from the group consisting of iliac arteries, femoral arteries, and popliteal arteries.
21. The method of claim 18 , wherein the anti-inflammatory agent is delivered at a dosage of 3.2 mg to 24 mg.
22. The method of claim 18 , wherein the anti-inflammatory agent is delivered at a dosage of 2.4 mg to 8.0 mg per infusion.
23. The method of claim 18 , wherein the delivered anti-inflammatory agent distributes completely circumferentially through the adventitial tissue surrounding the blood vessel at a delivery site.
24. The method of claim 21 , wherein the anti-inflammatory agent is delivered right after revascularization.
25. The method of claim 18 , further comprising delivering a contrast agent for visualization through the needle advanced into the adventitial tissue.
26. The method of claim 25 , wherein the anti-inflammatory agent is delivered with the contrast agent at a primary therapeutic agent to contrast ratio of 4:1.
27. The method of claim 18 , wherein the anti-inflammatory agent is incorporated into a lipophilic carrier or adjuvant.
28. The method of claim 18 , wherein the anti-inflammatory agent is delivered with saline.
29. The method of claim 18 , wherein the anti-inflammatory agent is incorporated into liposomes.
30. The method of claim 18 , wherein the anti-inflammatory agent is delivered with an erodable polymer.
31. The method of claim 18 , wherein the anti-inflammatory agent is delivered with a solubilizer.
32. The method of claim 18 , wherein the anti-inflammatory agent is provided as microparticles or nanoparticles.
33. The method of claim 18 , wherein the method further comprises withdrawing the needle from the adventitial tissue and withdrawing the catheter out of the blood vessel of patient after delivering the anti-inflammatory agent.