Methods and compositions for treatment of lesioned sites of body vessels
Methods and compositions for inducing apoptosis of cells, such as macrophages, at a lesioned site of a body vessel are disclosed herein. Nitric oxide can be directly or indirectly delivered to a treatment site to increase macrophage apoptosis. Delivery can include site specific delivery of nitric oxide gas, nitric oxide in aqueous solution or a substance(s) which releases nitric oxide or causes nitric oxide to be generated from an endogenous source. Delivery can be achieved by a delivery system such as a catheter assembly, stent or other suitable device.
1. A composition for inducing cell apoptosis at an atherosclerotic lesion in a blood vessel, comprising:
a mixture having a solvent and an amount of nitric oxide dissolved in the solvent, wherein the solvent is an aqueous solution selected from the group consisting of saline and physiological buffer, and wherein the aqueous solution is saturated with the amount of nitric oxide; and
a microsphere dispersed in the mixture, the microsphere having a polymer encapsulant encapsulating an unbound nitric oxide gas prior to being dispersed in the mixture; and
wherein the mixture is suitable for delivery into a blood vessel to deliver the microsphere to a cell in an atherosclerotic lesion in the blood vessel.
2. The composition of claim 1 , wherein the polymer encapsulant comprises poly(caprolactone).
3. The composition of claim 1 , wherein the amount of nitric oxide is less than about three thousandths of a mole per liter of the mixture.
4. The composition of claim 1 , wherein the mixture further comprises a surfactant selected from the group consisting of poly vinyl alcohol, poly vinyl pyrrolidone, lipids, amphiphilic polymers, and ionic surfactants.
5. A treatment kit comprising:
a delivery device comprising a catheter assembly having a delivery cannula, wherein the catheter assembly is sized and configured for insertion into a blood vessel; and
a nitric oxide source comprising a mixture having a solvent and an amount of nitric oxide dissolved in the solvent, and a microsphere dispersed in the mixture, the microsphere having a polymer encapsulant encapsulating an unbound nitric oxide gas prior to being dispersed in the mixture, wherein the solvent is an aqueous solution selected from the group consisting of saline and physiological buffer, wherein the aqueous solution is saturated with the amount of nitric oxide, and wherein the nitric oxide source is suitable for delivery through the delivery cannula into the blood vessel.
6. The treatment kit of claim 5 , wherein the polymer encapsulant comprises poly(caprolactone).
7. The treatment kit of claim 5 , wherein the amount of nitric oxide is less than about three thousandths of a mole per liter of the mixture.
8. The treatment kit of claim 5 , wherein the mixture further comprises a surfactant selected from the group consisting of poly vinyl alcohol, poly vinyl pyrrolidone, lipids, amphiphilic polymers, and ionic surfactants.