Nanoparticles for drug-delivery
AssigneeUniversity of South Florida
InventorsEdward Turos, Jeung-Yeop Shim
Life of this patent
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Abstract
This invention relates to polymeric nanoparticles useful for drug delivery with target molecules bonded to the surface of the particles and having sizes of up to 1000 nm, preferably 1 nm to 400 nm, more preferably 1 nm to 200 nm, that are dispersed homogeneously in aqueous solution. The target drug/target substance is covalently bonded to the novel polymeric nanoparticles to secure them from outer intervention in vivo or cell culture in vitro until they are exposed at the target site within the cell. This invention also relates to microemulsion polymerization techniques useful for preparing the novel nanoparticles.
Claims66
A process for preparing polymeric nanoparticles comprising i) or ii), wherein
- i):
- a) dissolving at least one modified bioaffecting agent in at least one polymerizable hydrocarbon monomer to form a homogenous solution;
- b) pre-emulsifying the homogenous solution with the addition of an emulsifier selected from the group consisting of anionic, cationic, nonionic emulsifiers, and a mixture of any of the foregoing, in an aqueous solution to form micelles having a hydrophobic core, wherein the monomer and the bioaffecting agent are entrapped within the hydrophobic core of the micelles;
- and
- c) initiating free-radical polymerization of the monomers and modified bioaffecting agent with the addition of a water-soluble initiator;
- and
- ii):
- d) dissolving at least one modified bioaffecting agent in at least one polymerizable hydrocarbon monomer to form a homogenous solution;
- e) pre-emulsifying the homogenous solution with the addition of an emulsifier selected from the group consisting of anionic, cationic nonionic emulsifiers, and a mixture of any of the foregoing, in an aqueous solution to form micelles having a hydrophobic core wherein the monomer and the bioaffecting agent are entrapped within the hydrophobic core of the micelles;
- f) initiating free-radical polymerization of the monomers and modified bioaffecting agent with the addition of a water-soluble initiator;
- and
- g) coalescing the aqueous solution for a sufficient period of time to form a dry polymer film comprising polymeric nanoparticles.
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The process according to claim 14, wherein the moiety is selected from the group consisting of dansyl chloride, 1 -naphtholic acid, and 9-anthracene-carboxylic acid.
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The process according to claim 20, wherein the linker functional group is cleaved enzymatically or chemically.
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A polymeric nanoparticle comprising:
- a) a nanoparticle, at least one bioaffecting agent arrayed around the surface of the nanoparticle, and a linker covalently bonding the bioaffecting agent to the nanoparticle:
- b) a nanoparticle, at least one bioaffecting agent arrayed around the surface of the nanoparticle, a linker covalently bonding the bioaffecting agent to the nanoparticle, and means for selecting a target cell;
- c) a nanoparticle, at least one bioaffecting agent arrayed around the surface of the nanoparticle, a linker covalently bonding the bioaffecting agent to the nanoparticle, and a sugar coating on the surface of the nanoparticle:
- or
- d) a nanoparticle;
- at least one bioaffecting agent arrayed around the surface of the nanoparticle;
- a linker covalently bonding the bioaffecting agent to the nanoparticle, and a target agent;
- wherein the bioaffecting agent is:
- 1) a water-insoluble solid or a liquid, wherein the liquid is soluble in an organic solution and not miscible in an aqueous solution;
- 2) selected from the group consisting of analgesics, anesthetics, anti-inflammatory agents, anthelmintics, anti-arrhythmic agents, antiasthma agents, antibiotics, anticancer agents, anticoagulants, antidepressants, antidiabetic agents, antiepileptics, antihistamines, antitussives, antihypertensive agents, antimuscarinic agents, antimycobacterial agents, antineoplastic agents, antioxidant agents, antipyretics, immunosuppressants, immunostimulants, antithyroid agents, antiviral agents, anxiolytic sedatives, astringents, bacteriostatic agents, beta-adrenoceptor blocking agents, blood products and substitutes, bronchodilators, buffering agents, cardiac inotropic agents, chemotherapeutics, contrast media, corticosteroids, cough suppressants, diagnostic agents, diagnostic imaging agents, diuretics, dopaminergics, free radical scavenging agents, growth factors, haemostatics, immunological agents, lipid regulating agents, muscle relaxants, proteins, peptides and polypeptides xanthines, alprazolam, amiodarone, amlodipine, astemizole, atenolol, azathioprine, azelatine, beclomethasone, β-lactam, budesonide, buprenorphine, butalbital, carbamazepine, carbidopa, cefotaxime, cephalexin, cholestyramine, ciprofloxacin, cisapride, cisplatin, clarithromycin, clonazepam, clozapine, cyclosporin, diazepam, diclofenac sodium, digoxin, dipyridamole, divalproex, dobutamine, doxazosin, enalapril, estradiol, etodolac, etoposide, famotidine, felodipine, fentanyl citrate, fexofenadine, finasteride, fluconazole, flunisolide, flurbiprofen, fluvoxamine, furosemide, glipizide, gliburide, ibuprofen, isosorbide dinitrate, isotretinoin, isradipine, itraconazole, ketoconazole, ketoprofen, lamotrigine, lansoprazole, loperamide, loratadine, lorazepam, lovastatin, medroxyprogesterone, mefenamic acid, methylprednisolone, midazolam, mometasone, nabumetone, naproxen, nicergoline, nifedipine, norfloxacin, omeprazole, paclitaxel, penicillin, phenytoin, piroxicam, quinapril, ramipril, risperidone, sertraline, simvastatin, steroids, taxol, terbinafine, terfenadine, triamcinolone, valproic acid, zolpidem, expectorants, mucolytics, hypnotics, neuroleptics, and a pharmaceutically acceptable salt of any of the foregoing,
- 3) a β-lactam selected from the group consisting of N-methylthiolated β-lactam, C-4 acrylate N-methylthiolated β-lactam C-3 polyester acrylate N-methylthiolated β-lactam, and bis-acrylated N-methylthiolated β-lactam, or
- 4) an antibiotic selected from the group consisting of ciprofloxacin, penicillin G, or sulindac.
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A method of delivering a bioaffecting agent to a cell comprising:
- a) administering a pharmaceutically effective amount of a polymeric nanoparticle to a cell in a host biosystem;
- b) administering a pharmaceutically effective amount of a polymeric nanoparticle to a cell in a host biosystem, and detecting the cell;
- c) administering a pharmaceutically effective amount of a polymeric nanoparticle to a cell in a host biosystem, detecting the cell and sending out a signal that the cell has been detected;
- d) administering a pharmaceutically effective amount of a polymeric nanoparticle to a cell in a host biosystem, and sequentially or simultaneously administering a drug;
- e) administering a pharmaceutically effective amount of a polymeric nanoparticle to a cell in a host biosystem, detecting the cell, and sequentially or simultaneously administering a drug;
- or
- f) administering a pharmaceutically effective amount of a polymeric nanoparticle to a cell in a host biosystem, detecting the cell, and sending out a signal that the cell has been detected, and sequentially or simultaneously administering a drug:
- wherein the polymeric nanoparticle comprises:
- 1) a nanoparticle, at least one bioaffecting agent arrayed around the surface of the nanoparticle, and a linker covalently bonding the bioaffecting agent to the nanoparticle;
- 2) a nanoparticle, at least one bioaffecting agent arrayed around the surface of the nanoparticle, a linker covalently bonding the bioaffecting agent to the nanoparticle, and a target agent;
- or
- 3) a nanoparticle, at least one bioaffecting agent arrayed around the surface of the nanoparticle, a linker covalently bonding the bioaffecting agent to the nanoparticle, and a fluorescing agent.
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A pharmaceutical composition comprising a polymeric nanoparticle in a pharmaceutical carrier, wherein the polymeric nanoparticle is associated with a bioaffecting agent.
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Dependencies are inferred from the claim text.