Drug delivery compositions including nanoshells for triggered drug release
The current invention is directed to compositions comprising a plurality of particles including nanoshells or a medical device with a coating including nanoshells allowing for triggered drug release. Methods of treatment with such compositions are also included.
1. A composition for controlled release of a drug comprising:
a plurality of particles comprising:
a polymer which is either an amorphous or semi-crystalline polymer with a glass transition temperature as plasticized under physiological conditions from about 40° C. to about 60° C., or a semi-crystalline polymer having a degree of crystallinity of at least 25% with a melting temperature, as plasticized under physiological conditions, from about 40° C. to about 60° C.;
a drug; and
one or more nanoshells capable of producing heat upon exposure to electromagnetic radiation, a fluctuating magnetic field, or a microwave field; wherein
substantially all of the individual particles of the plurality include one or more of the nanoshells;
wherein the particles comprise a polymer matrix comprising the polymer and coating the nanoshell; or the particles are composed of a polymer matrix comprising the polymer and nanoshells; or the particles comprise a polymer matrix comprising the polymer and nanoshells, the polymer matrix surrounding a central core; and
wherein upon exposure to electromagnetic radiation, or a fluctuating magnetic field, or a microwave field, the nanoshells produce sufficient heat to raise the temperature of the polymer above its glass transition temperature or its melting temperature.
2. The composition of claim 1 , wherein the glass transition temperature or the melting temperature of the polymer is from about 40° C. to about 50° C.
3. The composition of claim 1 , wherein the average diameter of the particles is about 50 nanometers to about 10 micrometers.
4. The composition of claim 1 , wherein the nanoshells comprise gold.
5. The composition of claim 4 , wherein the average diameter of the nanoshells is about 15 nanometers to about 200 nanometers.
6. The composition of claim 1 , wherein the nanoshells comprise cores comprising a metal selected from the group consisting of iron, iron oxide, lanthanides, samarium, gadolinium, europium, terbium, tantalum, molybdenum, alloys thereof, and combinations thereof.
7. The composition of claim 1 , wherein the nanoshells comprise a metal selected from the group consisting of silver, platinum, palladium, chromium, iridium, magnesium, zinc, calcium, tungsten, alloys thereof, and combinations thereof.
8. The composition of claim 1 , wherein the polymer is selected from the group consisting of poly(L-lactide-co-glycolide), poly(D,L-lactide), poly(L-lactide), polyglycolide, poly(D,L-lactide-co-glycolide), poly(glycolide), polycaprolactone, poly(lactide-co-caprolactone), poly(glycolide-co-caprolactone), biodegradable polyurethanes, poly(hydroxybutyrate), poly(hydroxyvalerate), poly(ethylene glycol), poly(ethylene glycol)-poly(L-lactide) diblock copolymers, poly(ethylene glycol)-poly(L-lactide-glycolide) diblock copolymers, poly(L-lactide-glycolide)-poly(ethylene glycol)-poly(L-lactide-glycolide) triblock copolymers, poly(hydroxybutyrate-co-valerate), block copolymers of poly(ethylene oxide) and polypropylene oxide), polyphosphoester urethane, poly(amino acids), poly(trimethylene carbonate), poly(ether-esters), polyphosphazenes, and combinations thereof.
9. The composition of claim 1 , wherein the drug is selected from the group consisting of actinomycins, taxol, paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutases mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), biolimus A9, deforolimus, AP23572, temsirolimus, pimecrolimus, 40-O-tetrazolyl-rapamycin, 40-epi-(N1-tetrazole)-rapamycin, pirfenidone, tacrolimus, dexamethasone, rapamycin, 40-O-(2-hydroxy)ethyl-rapamycin(everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin, zotarolimus, γ-hiridun, clobetasol, pimecrolimus, imatinib mesylate, midostaurin, and combinations thereof.
10. The composition of claim 1 , wherein the composition comprises at least two drugs, the two drugs comprising a statin and an anti-inflammatory drug, or a statin and fenofibrate.
11. The composition of claim 10 , wherein the composition is capable of releasing both drugs at an increased release rate after the composition is exposed to electromagnetic radiation, a fluctuating magnetic field, or a microwave field.
12. The composition of claim 1 , wherein the particles comprise a polymer matrix comprising the polymer, the polymer matrix coating the nanoshell.
13. The composition of claim 1 , wherein the particles comprise a polymer matrix comprising the polymer and nanoshells, the polymer matrix surrounding a central core.
14. The composition of claim 1 , whereby the increase in the temperature of the polymer of the particles results in a change in the diffusivity of the drug.
15. The composition of claim 1 , whereby the increase in the temperature of the polymer of the particles results in a change in the diffusivity of the drug, and wherein the drug release from the particles is impacted by the change in diffusivity of the drug.
16. A method comprising:
administering to a patient in need thereof the composition of claim 1 ; and
after administration, activating the particles of the composition by exposing the particles to a fluctuating magnetic field, a microwave field, or an electromagnetic radiation to the composition.
17. The method of claim 16 , wherein administering the composition comprises systemic or local administration.
18. The method of claim 17 , wherein systemic administration comprises intravenous injection, intramuscular injection, or injection into the bone marrow.
19. The method of claim 17 , wherein local administration comprises administration selected from the group consisting of administration by a catheter, a coated balloon catheter, a needle-injection catheter, a porous balloon catheter, local needle injection, implantation of a coated stem, implantation of a biodegradable stem, implantation of a biodegradable implant, and combinations thereof.
20. The method of claim 16 , wherein the source of the fluctuating magnetic field, the microwave field, or the electromagnetic radiation is outside the patient's body.
21. The method of claim 16 , wherein the source of the fluctuating magnetic field, the microwave field, or the electromagnetic radiation is inside the patient's body.
22. The method of claim 21 , where the source of the fluctuating magnetic field, the microwave field, or the electromagnetic radiation is in a cathether within the patient's body.
23. The method of claim 16 , wherein patient is need of treatment for a disease or condition selected from the group consisting of atherosclerosis, vulnerable plaque, restenosis, peripheral vascular disease, small vessel bifurcations and cancer.