Nanoparticles for Extravascular Administration
Disclosed are drug delivery systems and methods for extravascular administration of drug, vaccine, and/or diagnostic agents, for use in research and medical applications.
1 . A method of treating a disease or disorder, comprising administering to a subject in need of such treatment, a therapeutically effective amount of non-viral nanoparticles, wherein said nanoparticles comprise a micelle core comprising a bioactive macromolecule and a surfactant with an HLB value of less than or equal to about 6.0, a shell adsorbed to the micelle core and comprising a ligand and lithium, and having a mean diameter of less than about 50 nanometers, wherein;
(a) the bioactive macromolecule comprises an oligonucleotide, a protein, a peptide, a carbohydrate, or an antibody;
(b) the ligand comprises a protein, a peptide, a carbohydrate, an antibody, or a small molecule; and
(c) the nanoparticles are administered subcutaneously.
2 . The method of claim 1 , wherein the bioactive macromolecule comprises an oligonucleotide or a therapeutic plasmid.
3 . The method of claim 2 , wherein the bioactive macromolecule comprises an oligonucleotide, and the dose administered of the oligonucleotide is less than or equal to about 5 mg/kg.
4 . The method of claim 3 , wherein the ligand is Asialoorosomucoid (ASOR).
5 . The method of claim 2 , wherein the bioactive macromolecule comprises a therapeutic plasmid, and wherein the administering comprises repeat dosing.
6 . The method of claim 2 , wherein the bioactive macromolecule comprises a therapeutic plasmid, and wherein the dose administered of the plasmid is greater than or equal to about 10 mg/kg.
7 . A pharmaceutical composition comprising non-viral nanoparticles comprising a micelle core comprising an antigen and a surfactant with an HLB value of less than or equal to about 6.0, a shell adsorbed to the micelle core and comprising a ligand, lithium, and an adjuvant, and having a mean diameter of less than about 50 nanometers, wherein;
(a) the antigen is hydrophilic and comprises a DNA plasmid, a protein, or a peptide;
(b) the adjuvant comprises nickel; and
(c) the ligand comprises hyaluronan, wherein said hyaluronan ligand has an average molecular weight of less than about 50,000 Daltons and is non-covalently attached to the nanoparticles.
8 . The composition of claim 7 , wherein the composition is for inducing an immune response in a subject.
9 . A method of inducing an immune response in a subject, comprising administering to the subject a therapeutically effective amount of the composition of claim 7 , wherein the composition is topically administered.
10 . A composition for imaging a subject, said composition comprising non-viral nanoparticles comprising a micelle core comprising an imaging agent, wherein the imaging agent is dysprosium, and a surfactant with an HLB value of less than or equal to about 6.0, a shell adsorbed to the micelle core and comprising a ligand and lithium, and having a mean diameter of less than about 50 nanometers.
11 . The composition of claim 10 , where the dysprosium is chelated to a DOTA-Dextran conjugate.
12 . The composition of claim 10 , wherein the subject is a human.