Methods and kits for delivering pharmaceutical agents into the coronary vascular adventitia
Methods and kits for delivering pharmaceutical agents to the adventitia surrounding a blood vessel utilize a catheter having a microneedle. The microneedle is positioned in the perivascular space and delivers an amount of pharmaceutical agent sufficient to circumferentially permeate around the blood vessel and, in many cases, extend longitudinally along the blood vessel and in some cases to the adventitia surrounding other blood vessels.
1 . A method for distributing an angiogenesis agent in the adventitial tissue of a living vertebrate host, said method comprising:
positioning a microneedle through the wall of a blood vessel so that an aperture of the microneedle is positioned in a perivascular space surrounding the blood vessel; and
delivering an amount of the angiogenesis agent into the perivascular space so that the agent distributes substantially completely circumferentially through adventitial tissue surrounding the blood vessel at the site of the microneedle.
2 . A method as in claim 1 , wherein the agent distributes longitudinally along the blood vessel over a distance of at least 1 cm within a time period no greater than 60 minutes so that the concentration of agent in the adventitia at a location spaced 2 cm longitudinally from the delivery site is at least 10% of the concentration at the delivery site.
3 . A method as in claim 1 , wherein the aperture of the microneedle is positioned at a distance from an inner wall of the blood vessel equal to at least 10% of the mean luminal diameter of the blood vessel at the microneedle site.
4 . A method as in claim 3 , wherein the distance from the inner wall is from 10% to 75% of the mean luminal diameter.
5 . A method as in claim 1 , wherein the agent comprises angiogenesis genes.
6 . A method as in claim 1 , wherein the agent increases microvasculature of one of the pericardium, vaso vasorum, or adventitia to increase blood flow.
7 . A method as in claim 1 , wherein the agent distributes into regions of the adventitia surrounding other blood vessels.
8 . A method as in claim 1 , wherein the amount of the agent is in the range from 10 μl to 5000 μl.
9 . A method as in claim 1 , wherein the agent distributes from the adventitia transmurally back into the intima.
10 . A method as in claim 1 , wherein the blood vessel is a coronary blood vessel.
11 . A method as in claim 10 , wherein the coronary blood vessel is an artery.
12 . A method as in claim 11 , wherein the coronary artery is at risk of hyperplasia.
13 . A method as in claim 11 , wherein the coronary artery has regions of vulnerable plaque.
14 . A method as in claim 1 , wherein the patient is suffering from congestive heart failure or a cardiac arrhythmia.
15 . A method for depoting an angiogenesis agent in the adventitial tissue of a living vertebrate host's heart, said method comprising:
positioning a microneedle through the wall of a coronary blood vessel so that an aperture of the microneedle is positioned in a perivascular space surrounding the blood vessel; and
delivering an amount of the angiogenesis agent into the perivascular space so that the agent distributes within adventitial tissue surrounding the blood vessel to provide a depot of agent which is released back into the blood vessel wall over time.
16 . A method as in claim 15 , wherein the agent distributes longitudinally along the blood vessel over a distance of at least 1 cm within a time period no greater than 60 minutes so that the concentration of agent in the adventitia at a location spaced 2 cm longitudinally from the delivery site is at least 10% of the concentration at the delivery site.
17 . A method as in claim 15 , wherein the aperture of the microneedle is positioned at a distance from an inner wall of the blood vessel equal to at least 10% of the mean luminal diameter of the blood vessel at the microneedle site.
18 . A method as in claim 17 , wherein the distance from the inner wall is from 10% to 75% of the mean luminal diameter.
19 . A method as in claim 15 , wherein the agent comprises angiogenesis genes.
20 . A method as in claim 15 , wherein the agent increases microvasculature of one of the pericardium, vaso vasorum, or adventitia to increase blood flow.
21 . A method as in claim 15 , wherein the agent distributes into regions of the adventitia surrounding other blood vessels.
22 . A method as in claim 15 , wherein the amount of the agent is in the range from 10 μl to 5000 μl.
23 . A method as in claim 15 , wherein the coronary blood vessel is an artery.
24 . A method as in claim 23 , wherein the coronary artery is at risk of hyperplasia.
25 . A method as in claim 23 , wherein the coronary artery has regions of vulnerable plaque.