Delivery compositions, and methods of making and using same
This invention provides compositions comprising at least one protein nanoparticle comprising a protein and a stealth polymer. In certain embodiments, the nanoparticle further comprises a therapeutic agent, such as a miRNA and/or siRNA. In other embodiments, the nanoparticle further comprises a cell surface receptor ligand. Also included in the invention are methods of preparing the compositions of the present invention, and methods of treating, ameliorating or preventing a disease or disorder in a subject in need thereof using the compositions of the present invention.
1 . A method of treating, or ameliorating a disease or disorder in a subject in need thereof, the method comprising administering to the subject a pharmaceutically effective amount of a nanoparticle,
wherein the nanoparticle comprises:
a nanoparticle core comprising at least one protein, which is at least one of the following:
a plasma protein selected from the group consisting of an albumin, a fibrinogen, and a globulin,
an IgG,
a cytokine selected from the group consisting of interleukin, erythropoietin, interferon, and filgrastim,
an immunomodulator which is cyclosporine,
a hormone selected from the group consisting of insulin, glucagon, and somatotropin, and
an enzyme selected from the group consisting of a blood clotting factor, an adenosine deaminase, and alpha-1 antitryptin;
a stealth polymer layer comprising a stealth polymer and surrounding the nanoparticle core; and
an aptamer;
wherein the at least one protein in the nanoparticle core is in a neutral state in the nanoparticle;
wherein the aptamer is covalently conjugated with the at least one protein in the nanoparticle core;
wherein at least a fraction of the aptamer is displayed on the outer surface of the nanoparticle; and
wherein the nanoparticle is administered to the subject by an intrapulmonary, intrabronchial, inhalational, intranasal, intratracheal, intravenous, intramuscular, subcutaneous, topical, transdermal, oral, buccal, rectal, pleural, peritoneal, vaginal, epidural, otic, intraocular, or intrathecal route.
2 . The method of claim 1 , wherein the aptamer binds to at least one selected from the group consisting of neurotensin receptor-1, human epidermal growth factor receptor-2 (HER-2), folate receptor, insulin-like growth receptor (IGF), and epidermal growth factor receptor (EGFR).
3 . The method of claim 1 , wherein the disease or disorder is selected from the group consisting of colon cancer, rectum cancer, lung cancer, glioblastoma, renal cell cancer, non-small cell lung cancer, small cell lung cancer, asthma, respiratory syncytial virus (RSV) infection, and any combinations thereof.
4 . The method of claim 1 , wherein the stealth polymer is at least one selected from the group consisting of alkyl polyethylene oxide, an alkyl polyethylene glycol, an alkylphenol oxide, a copolymer of polyethylene glycol and polypropylene oxide, a polyethylene glycol, a polypropylene glycol, a polyvinylpyrrolidone (PVP), and a polyvinyl alcohol.
5 . The method of claim 4 , wherein the alkyl polyethylene oxide comprises at least one selected from the group consisting of a diethylene glycol hexadecyl ether, polyethylene glycol oleyl ether, diethylene glycol octadecyl ether, polyoxyethylene stearyl ether, polyethylene glycol hexadecyl (cetyl) ether, polyethylene glycol dodecyl (lauryl) ether, decaethylene glycol oleyl ether, polyethylene glycol octadecyl ether, and polyethylene glycol octadecyl ether.
6 . The method of claim 1 , wherein the nanoparticle has a diameter ranging from about 10 nm to about 1,000 nm.
7 . The method of claim 1 , wherein the nanoparticle further comprises at least one therapeutic agent.
8 . The method of claim 7 , wherein the at least one therapeutic agent comprises at least one selected from the group consisting of an organic compound, inorganic compound, pharmacological drug, antibody, radiopharmaceutical, protein, peptide, polysaccharide, nucleic acid, siRNA, miRNA, RNAi, short hairpin RNA, antisense nucleic acid, ribozyme and dominant negative mutant.
9 . The method of claim 8 , wherein the antibody comprises at least one monoclonal antibody selected from the group consisting of bevacizumab, anatumomab, benralizumab, enokizumab, mitumomab, oxelumab, and palivizumab.
10 . The method of claim 7 , wherein the at least one therapeutic agent comprises a siRNA or miRNA, and wherein the at least one protein in the nanoparticle core comprises IgG.