Methods for producing nanoparticles
The present invention relates to methods of preparing nanoparticles from reactively formed block and/or graft copolymers and nanoparticles derived therefrom
1 . A method of producing nanoparticles, the method comprising:
providing a first reactant mixture comprising a first solvent stream and one or more polymeric reactants, wherein the first solvent stream comprises one or more solvents;
providing a second reactant mixture comprising a second solvent stream and one or more polymeric reactants, wherein the second solvent stream comprises one or more solvents; and
combining the reactant mixtures and flash precipitating under conditions to react the polymeric reactants and form precipitated nanoparticles comprising a block and/or graft copolymer.
2 . The method of claim 1 wherein flash precipitating the nanoparticles is performed in a centripetal mixer, a continuous flash mixer, or a batch flash mixer.
3 . The method of claim 2 wherein the mixing velocity has a Reynold's number of at least 100.
4 . The method of claim 1 wherein the concentration of the polymeric reactant in each reactant mixture is at least 0.1 wt-%.
5 . The method of claim 1 wherein the nanoparticles have a polydispersity index of less than 2.
6 . The method of claim 1 wherein the nanoparticles have an average particle size of less than 1000 nm.
7 . The method of claim 1 wherein at least one of the reactant mixtures comprises a polymeric reactant selected from functionalized polystyrenes, functionalized polycaprolactones, polyacrylates, functionalized polyethyleneglycols, polyglutamic acids, hyaluronic acids, functionalized polyvinylpyrrolidones, polylysines, polyspermines, polyarginines, alginic acids, functionalized polylactides, polyethyleneimines, polyacrylic acids, polyiminocarboxylates, and mixtures thereof.
8 . The method of claim 7 wherein at least one of the reactant mixtures comprises a polymeric reactant selected from functionalized polystyrenes, functionalized polycaprolactones, and mixtures thereof.
9 . The method of claim 7 wherein at least one of the reactant mixtures comprises a polymeric reactant selected from functionalized polyethylene glycols and mixtures thereof.
10 . The method of claim 1 wherein at least one of the reactant mixtures comprises one or more polymeric reactants functionalized with an acid chloride group, an isocyanate group, an anhydride group, an epoxide group, a ketone group, an aldehyde group, an enone group, enoate group, an alkyne group, another electrophilic group, or mixtures thereof.
11 . The method of claim 1 wherein at least one of the reactant mixtures comprises one or more polymeric reactants functionalized with an amino group, a hydroxyl group, a carboxylic acid group, a hydrazine group, a hydroxylamino group, a thiol group, an aromatic group, a heteroaromatic group, another nucleophilic group, or mixtures thereof.
12 . The method of claim 1 further comprising providing one or more additional solvent streams comprising one or more solvents.
13 . The method of claim 1 further comprising providing a third reactant mixture comprising a third solvent stream and one or more polymeric reactants, wherein the third solvent stream comprises one or more solvents.
14 . The method of claim 1 further comprising a step of removing the solvents from the resultant mixture comprising the nanoparticles.
15 . The method of claim 14 wherein the solvents are removed by a process selected from the group consisting of filtration, distillation, evaporation, expansion, spray drying, lyophilization, centrifugation, extraction, and combinations thereof.
16 . The method of claim 1 further comprising providing one or more additive target molecules.
17 . The method of claim 16 wherein providing one or more additive target molecules comprises providing the one or more additive target molecules in one or more of the reactant mixtures.
18 . The method of claim 16 wherein providing one or more additive target molecule comprises providing the one or more additive target molecules in one or more solvent streams.
19 . The method of claim 16 wherein the block and/or graft copolymer and the one or more additive target molecules are present in the nanoparticles in a ratio of at least 1:20 by weight.
20 . The method of claim 16 wherein the block and/or graft copolymer and the one or more additive target molecules are present in the nanoparticles in a ratio of no greater than 99:1 by weight.
21 . The method of claim 16 wherein at least one additive target molecule is selected from the group consisting of pharmaceutical actives and pharmaceutical precursor compounds.
22 . The method of claim 16 wherein at least one additive target molecule is selected from the group consisting of cyclosporins, immunoactive agents, analgesics, anti-inflammatory agents, anthelmintics, anti-arrhythmic agents, antibiotics, anticoagulants, antidepressants, antidiabetic agents, antiepileptics, antihistamines, antihypertensive agents, antimuscarinic agents, antimycobacterial agents, antineoplastic agents, immunosuppressants, antithyroid agents, antiviral agents, anxiolytic sedatives, astringents, beta-adrenoceptor blocking agents, blood products and substitutes, cardiac inotropic agents, contrast media, corticosteroids, cough suppressants, diagnostic agents, diagnostic imaging agents, diuretics, dopaminergics, haemostatics, immuriological agents, lipid regulating agents, muscle relaxants, parasympathomimetics, parathyroid calcitonin and biphosphonates, prostaglandins, radio-pharmaceuticals, sex hormones, anti-allergic agents, stimulants and anoretics, sympathomimetics, thyroid agents, vasodilators, xanthines, antioxidants, preservatives, vitamins, nutrients, and combinations thereof.
23 . The method of claim 16 wherein at least one additive target molecule is a peptide.
24 . The method of claim 16 wherein at least one additive target molecule is selected from the group consisting of biocides, pesticides, herbicides, fungicides, insecticides, and combinations thereof.
25 . The method of claim 16 wherein at least one additive target molecule is selected from the group consisting of cosmetic products, dyes, salts, biological markers, biological imaging agents, ink pigments, magnetic particles, radiopaque materials, and combinations thereof.
26 . The method of claim 16 further comprising a step of removing the solvents from the resultant mixture comprising the nanoparticles.
27 . The method of claim 26 wherein the solvents are removed by a process selected from the group consisting of filtration, distillation, evaporation, expansion, spray drying, lyophilization, centrifugation, extraction, and combinations thereof.
28 . The method of claim 1 further comprising providing one or more supplemental additives.
29 . Nanoparticles prepared according to the process of claim 1 .
30 . Nanoparticles prepared according to the process of claim 16.