Drug-eluting insertable medical device for treating acute myocardial infarction, thrombus containing lesions and saphenous-vein graft lesions
A method for delivering at least one drug at a target site in a blood vessel for treating at least one of an acute myocardial infarction, a thrombus containing lesion and a saphenous-vein graft lesion is disclosed. The method includes delivering nano-carriers at the target site. The nano-carriers include one or more drugs encapsulated with a first biological agent. The nano-carriers further include a second biological agent in contact with one or more of the first biological agent and the one or more drugs. The first biological agent and the second biological agent have a first dissolution rate and a second dissolution rate respectively. The first dissolution rate is different from the second dissolution rate. The one or more drugs are released at the target site from the nano-carriers at a first release rate and a second release rate in response to dissolution of the first biological agent and the second biological agent, respectively.
1. A method for delivering at least one drug at a target site in a blood vessel at two different rates, comprising:
coating a surface of an insertable medical device with nano-crystals having an average diameter of approximately 157 nanometers, the nano-crystals comprising dexamethasone encapsulated with first nano-particles;
the first nano-particles comprising egg lecithin with 80% phosphatidylcholine;
coating the nano-crystals at least in part with second nano-particles, each of the second nano-particles in contact with either the dexamethasone or a nano-particle of the first nano-particles;
the second nano-particles comprising tricalcium phosphate hydrate;
implanting the insertable medical device coated with the nano-crystals at the target site in the blood vessel;
wherein upon exposure to the target site in the blood vessel, the tricalcium phosphate hydrate of the second nano-particles dissolves immediately at a pH below 7.4 to provide a burst release of the dexamethosone, thereby exposing the first nano-particles to the target site in the blood vessel after the second nano-particles have dissolved; and
wherein upon exposure to the target site in the blood vessel, the first nano-particles provide a prolonged release of the dexamethasone.
2. The method of claim 1 , further comprising nano-crystals of a second drug selected from the group consisting of a dexamethasone, a genistine, a flavenoid, a neoflavone, a aurone, a chalcone, a dihydrochalcone, a flavonol, a dihydroflavonol, a flavone, a flavanol, a isoflavone, a anthocyanidin, a proanthocyanidin, a isoflavane, a heparin, and a beta-estradiol, a sulphated glycosaminoglycan, heparin, heparin sulphate, dermatan sulphate, chondroitin sulphate, a derivative or conjugate of sulphated glycosaminoglycan, an anti-thrombin, an anti-proliferative agent, metotrexate, mitomycin C, doxyrubicin, a somatostatin analog, cytoschalasin B, rapamycin, cyclosporin, glucocorticoid (e.g. dexamethasone, betamethasone), hirudin, a tocopherol, an angiopeptin, dexamethasone sodium phosphate, a thrombin modulator such as pyridine, pyridine N-oxide, methylprednisolone, sulfasalazine, vincristine, vinblastine, fluorouracil, doxorubicin hydrochloride, an anticoagulant, an antifibrin, an antithrombin, sodium heparin, a low molecular weight heparin, a heparinoid, hirudin, argatroban, forskolin, vapiprost, a prostacyclin, a prostacyclin analogue, dextran, a D-phe-pro-arg-chloromethylketone (synthetic antithrombin), dipyridamole, a glycoprotein IIIb/IIIa platelet membrane receptor antagonist, an antibody, a recombinant hirudin, bivalirudin, an angiopeptin, an antimitotic agent, and an oligonucleotide.
3. The method of claim 1 , wherein the target site is at least one of a lesion and a thrombus in the blood vessel.
4. The method of claim 1 , wherein the insertable medical device is one of a stent, a balloon, a balloon catheter, and a thrombus aspiration catheter.
5. An insertable medical device for delivering at least one drug at a target site in a blood vessel at two or more different rates comprising:
a surface of the insertable medical device;
nano-crystals having an average diameter of approximately 157 nanometers distributed on the surface, the nano-crystals comprising dexamethasone encapsulated with first nano-particles;
the first nano-particles comprising egg lecithin with 80% phosphatidylcholine;
second nano-particles, each of the second nano-particles in contact with either the dexamethasone or a nano-particle of the first nano-particles;
the second nano-particles comprising tricalcium phosphate hydrate;
wherein upon exposure to the target site in the blood vessel, the tricalcium phosphate hydrate of the second nano-particles dissolves immediately at a pH below 7.4 to provide a burst release of the dexamethosone, thereby exposing the first nano-particles to the target site in the blood vessel after the second nano-particles have dissolved; and
wherein upon exposure to the target site in the blood vessel, the first nano-particles provide a prolonged release of the dexamethasone.
6. The drug-eluting insertable medical device of claim 5 , wherein the drug eluting insertable medical device is one of a stent, a balloon, a balloon catheter, and a thrombus aspiration catheter.