SONOLYSIS WITH BIODEGRADABLE NANOPARTICLES
The present invention provides methods for lysing a thrombus or ablating a mass in a subject by administering a plurality of biodegradable nanoparticles and delivering ultrasound to the subject. Also provided is a method for delivering a therapeutic agent to a tumor in a subject by administering a plurality of biodegradable nanoparticles comprising the therapeutic agent and delivering ultrasound to the subject.
1 . A method for lysing a thrombus in a subject in need thereof, the method comprising administering a plurality of biodegradable nanoparticles having an average diameter less than about 500 nm to the subject; and delivering ultrasound to the subject such that the thrombus is lysed.
2 . The method of claim 1 , wherein the plurality of biodegradable nanoparticles comprises a material chosen from a polysaccharide, a protein, a synthetic biodegradable polymer, or a combination thereof, and wherein the polysaccharide is chosen from starch, cellulose, pectin, chitosan, or a combination thereof; the protein is chosen from gelatin, collagen, albumin, or a combination thereof; and the synthetic biodegradable polymer is chosen from poly-lactide, poly-D-L-glycolide, poly-D-L-lactide-coglycolide, poly-ε-caprolactone, polyalkylenglycol, 1,3-propanediol, 1,4-butanediol, polycyanoacrylate, polyalkylcyanoacrylate, polyanhydride, polyorthoester, or a combination thereof.
3 . (canceled)
4 . The method of claim 1 , wherein the plurality of biodegradable nanoparticles comprises starch nanoparticles.
5 . The method of claim 4 , wherein the average diameter of the starch nanoparticles is about 200 nm.
6 . The method of claim 4 , wherein the average diameter of the starch nanoparticles is about 100 nm.
7 . The method of claim 1 , wherein the plurality of biodegradable nanoparticles is administered intra-arterially or intravenously.
8 . The method of claim 1 , wherein the thrombus is due to venous thrombosis, arterial thrombosis, stroke, myocardial infarction, endothelial cell injury, or disturbed blood flow.
9 . The method of claim 1 , wherein the plurality of biodegradable nanoparticles further comprise a thrombolytic agent chosen from tissue plasminogen activator, recombinant tissue plasminogen activator, anistreplase, streptokinase, and urokinase.
10 . The method of claim 1 , further comprising administering a thrombolytic agent chosen from tissue plasminogen activator, recombinant tissue plasminogen activator, anistreplase, streptokinase, and urokinase to the subject.
11 . The method of claim 1 , wherein the subject is a human.
12 . A method for ablating a mass in a subject in need thereof, the method comprising administering a plurality of biodegradable nanoparticles having an average diameter less than about 500 nm to the subject; and delivering ultrasound to the subject such that the mass is ablated.
13 . The method of claim 12 , wherein the mass is a tumor, an atherosclerotic plaque, a uterine fibroid, a renal calculus, a gallstone, or a polyp.
14 . The method of claim 12 , wherein the plurality of biodegradable nanoparticles comprises a material chosen from a polysaccharide, a protein, a synthetic biodegradable polymer, or a combination thereof, and wherein the polysaccharide is chosen from starch, cellulose, pectin, chitosan, or a combination thereof; the protein is chosen from gelatin, collagen, albumin, or a combination thereof; and the synthetic biodegradable polymer is chosen from poly-lactide, poly-D-L-glycolide, poly-D-L-lactide-coglycolide, poly-ε-caprolactone, polyalkylenglycol, 1,3-propanediol, 1,4-butanediol, polycyanoacrylate, polyalkylcyanoacrylate, polyanhydride, polyorthoester, or a combination thereof.
15 . (canceled)
16 . The method of claim 12 , wherein the plurality of biodegradable nanoparticles comprises starch nanoparticles.
17 . The method of claim 16 , wherein the average diameter of the starch nanoparticles is about 200 nm.
18 . (canceled)
19 . A method for delivering a therapeutic agent to a tumor in a subject in need thereof, the method comprising administering a plurality of biodegradable nanoparticles comprising the therapeutic agent and having an average diameter less than about 500 nm to the subject; and delivering ultrasound to the subject such that the therapeutic agent is delivered to the tumor.
20 . The method of claim 19 , wherein the therapeutic agent is chosen from alkylating agent, an anti-metabolite, an anti-tumor antibiotic, an anti-cytoskeletal agent, a topoisomerase inhibitor, an anti-hormonal agent, a targeted therapeutic agent, a radioisotope, or combinations thereof.
21 . The method of claim 19 , wherein the plurality of biodegradable nanoparticles comprises a material chosen from a polysaccharide, a protein, a synthetic biodegradable polymer, or a combination thereof, and wherein the polysaccharide is chosen from starch, cellulose, pectin, chitosan, or a combination thereof; the protein is chosen from gelatin, collagen, albumin, or a combination thereof; and the synthetic biodegradable polymer is chosen from poly-lactide, poly-D-L-glycolide, poly-D-L-lactide-coglycolide, poly-ε-caprolactone, polyalkylenglycol, 1,3-propanediol, 1,4-butanediol, polycyanoacrylate, polyalkylcyanoacrylate, polyanhydride, polyorthoester, or a combination thereof.
22 . (canceled)
23 . The method of claim 19 , wherein the plurality of biodegradable nanoparticles comprises starch nanoparticles.
24 . The method of claim 23 , wherein the average diameter of the starch nanoparticles is about 200 nm.
25 . (canceled)