Compositions and methods for drug delivery
The present disclosure is directed to surface-modified particles and to methods of making and using the same. The surface-modified particles comprise a particle core and a coating associated with the particle core, wherein the particle core comprises an active agent, the coating comprises an opsonin, and the surface-modified particle has an average size from about 1 nm to about 2,000 nm.
1. A pharmaceutical composition comprising a suspension containing a surface-modified particle, said surface-modified particle comprising a particle core and a coating associated with the particle core, said coating being adsorbed to a surface of the particle core, wherein the particle core comprises a therapeutic agent, the coating comprises an opsonin, the particle core is negatively charged, the particle core has hydrophobic regions on the particle core surface, the surface-modified particle has an average size from about 1 nm to about 2,000 nm, the pH of the suspension is below the isoelectric point of the opsonin, and the opsonin is selected from the group consisting of an antibody having an isotype of IgG, complement protein C3b, and complement protein C5.
2. The pharmaceutical composition of claim 1 , said coating being adsorbed to a surface of the particle core and further comprising a polysaccharide, and said opsonin being covalently attached to the polysaccharide.
3. The pharmaceutical composition of claim 2 , wherein the polysaccharide is dextran.
4. The pharmaceutical composition of claim 2 , wherein the polysaccharide has a molecular weight between about 5,000 daltons and about 250,000 daltons.
5. The pharmaceutical composition of claim 1 , wherein the coating further comprises a surfactant.
6. The pharmaceutical composition of claim 5 , wherein the surfactant is selected from the group consisting of anionic surfactants, cationic surfactants, zwitterionic surfactants, nonionic surfactants, surface active biological modifiers, and combinations thereof.
7. The pharmaceutical composition of claim 5 , wherein the surfactant comprises at least one of a poloxamer and a phospholipid.
8. The pharmaceutical composition of claim 1 , wherein the therapeutic agent is selected from the group consisting of analgesics, anesthetics, analeptics, adrenergic agents, adrenergic blocking agents, adrenolytics, adrenocorticoids, adrenomimetics, anticholinergic agents, anticholinesterases, anticonvulsants, alkylating agents, alkaloids, allosteric inhibitors, anabolic steroids, anorexiants, antacids, antidiarrheals, antidotes, antifolics, antipyretics, antirheumatic agents, psychotherapeutic agents, neural blocking agents, anti-inflammatory agents, antihelmintics, antibiotics, anticoagulants, antidepressants, antiepileptics, antifungals, anti-infective agents, anti-parasitic agents, antihistamines, antimuscarinic agents, antimycobacterial agents, antineoplastic agents, antiprotozoal agents, antiviral agents, anxiolytic sedatives, beta-adrenoceptor blocking agents, corticosteroids, cough suppressants, dopaminergics, hemostatics, hematological agents, hypnotics, immunological agents, muscarinics, parasympathomimetics, prostaglandins, radio-pharmaceuticals, sedatives, stimulants, sympathomimetics, vitamins, xanthines, growth factors, hormones, antiprion agents, and combinations thereof.
9. The pharmaceutical composition of claim 1 , wherein the therapeutic agent is an antineoplastic agent selected from the group consisting of paclitaxel, paclitaxel derivative compounds, alkaloids, antimetabolites, enzyme inhibitors, alkylating agents, and combinations thereof.
10. The pharmaceutical composition of claim 1 , wherein the therapeutic agent is a protease inhibitor.
11. The pharmaceutical composition of claim 10 , wherein the protease inhibitor is selected from the group consisting of indinavir, ritonavir, saquinavir, nelfinavir, and combinations thereof.
12. The pharmaceutical composition of claim 1 , wherein the therapeutic agent is a nucleoside reverse transcriptase inhibitor.
13. The pharmaceutical composition of claim 12 , wherein the nucleoside reverse transcriptase inhibitor is selected from the group consisting of zidovudine, didanosine, stavudine, zalcitabine, lamivudine and combinations thereof.
14. The pharmaceutical composition of claim 1 , wherein the therapeutic agent is a non-nucleoside reverse transcriptase inhibitor.
15. The pharmaceutical composition of claim 14 , wherein the non-nucleoside reverse transcriptase inhibitor is selected from the group consisting of efavirenz, nevirapine, delaviradine, and combinations thereof.
16. The pharmaceutical composition of claim 1 , wherein the therapeutic agent is an anti-inflammatory agent.
17. The pharmaceutical composition of claim 16 , wherein the anti-inflammatory agent is selected from the group consisting of non-steroidal anti-inflammatory drugs, non-selective cycloxygenase (COX) inhibitors, COX-1 inhibitors, COX-2 inhibitors, lipoxygenase inhibitors, corticosteroids, anti-oxidants, tumor necrosis factor (TNF) inhibitors, and combinations thereof.
18. The pharmaceutical composition of claim 1 , wherein the therapeutic agent is selected from the group consisting of celecoxib, rofecoxib, valdecoxib, parecoxib, lumiracoxib, etoricoxib, and combinations thereof.
19. The pharmaceutical composition of claim 1 , wherein the therapeutic agent is a biologic.
20. The pharmaceutical composition of claim 19 , wherein the biologic is selected from the group consisting of proteins, polypeptides, carbohydrates, polynucleotides, nucleic acids, and complexes, conjugates, and combinations thereof.
21. The pharmaceutical composition of claim 1 , wherein the therapeutic agent is a pharmaceutical compound.
22. The pharmaceutical composition of claim 1 , wherein the opsonin is human IgG.
23. The pharmaceutical composition of claim 1 , wherein the opsonin is intravenous immunoglobulin (IVIG).