Multi-compartmental macrophage delivery
Disclosed are multi-compartmental nanoparticulate systems for imaging as well as the diagnosis, monitoring, and treatment of inflammation and/or disease. These multicompartmental nanoparticulate systems can be used to target specific cells or cellular structures. Furthermore, these systems are capable of simultaneous delivery of hydrophilic and lipophilic compositions. Finally, these systems also allow for temporal control of drug delivery.
1. A method of imaging a macrophage with a multicompartment delivery system, the method comprising:
(a) administering an effective amount of the multicompartment delivery system to a subject, the multicompartment delivery system comprising one or more inner aqueous compartments encapsulated within an outer hydrophobic compartment, the outer hydrophobic compartment encapsulated in an exterior aqueous compartment; wherein the one or more inner aqueous compartments comprise a nanoparticle consisting of a polymeric matrix, at least one imaging agent, and optionally at least one therapeutic agent; and wherein the outer hydrophobic compartment is 0.5 to 20 microns in size and comprises an oil;
(b) allowing the multicompartment delivery system to deliver the imaging agent to a macrophage; and
(c) detecting the imaging agent in the subject.
2. The method of claim 1 , wherein the imaging agent is selected from the group consisting of colloidal gold, iron-oxide crystals, and quantum dots.
3. The method of claim 1 , wherein the imaging agent is selected from the group consisting of fluorophores, radiolabels, X-ray contrast agents, and positron emission tomographic agents.
4. The method of claim 1 , wherein the imaging agent is a fluorophore.
5. The method of any one of claims 2 , 3 , and 4 , wherein the nanoparticle consists of a polymeric matrix, an imaging agent, and a therapeutic agent.
6. The method of claim 1 , wherein the nanoparticle consists of a polymeric matrix and two imaging agents.
7. The method of claim 6 , wherein each of the imaging agents is selected from the group consisting of fluorophores, radiolabels, X-ray contrast agents, and positron emission tomographic agents.
8. The method of claim 5 , wherein the therapeutic agent is selected from the group consisting of chemotherapeutics, antibiotics, antivirals, small molecules, anti-inflammatory agents, siRNA, and DNA.
9. The method of claim 1 , wherein the polymeric matrix comprises poly(epsiloncaprolactone), gelatin, or alginate.
10. The method of claim 1 , wherein the polymeric matrix is hydrophilic.
11. The method of claim 1 , wherein the oil is safflower oil.
12. A method of treating a disease with a multicompartment delivery system for targeting a macrophage, the method comprising:
(a) administering an effective amount of the multicompartment delivery system to a subject, the multicompartment delivery system comprising one or more inner aqueous compartments encapsulated within an outer hydrophobic compartment, the outer hydrophobic compartment encapsulated in an exterior aqueous compartment; wherein the one or more inner aqueous compartments comprise a nanoparticle consisting of a polymeric matrix, at least one therapeutic agent, and optionally at least one imaging agent; and wherein the outer hydrophobic compartment is 0.5 to 20 microns in size and comprises an oil; and
b) allowing the multicompartment delivery system to deliver the therapeutic agent to a macrophage.
13. The method of claim 12 , wherein the disease is selected from the group consisting of atherosclerosis, Crohn's disease, inflammatory bowel disease, rheumatoid arthritis and cancer.
14. The method of claim 12 , wherein the nanoparticle consists of a polymeric matrix, an imaging agent, and at least one therapeutic agent.
15. The method of claim 14 , wherein the imaging agent is selected from the group consisting of colloidal gold, iron-oxide crystals, and quantum dots.
16. The method of claim 14 , wherein the imaging agent is selected from the group consisting of fluorophores, radiolabels, X-ray contrast agents, and positron emission tomographic agents.
17. The method of claim 14 , wherein the imaging agent is a fluorophore.
18. The method of claim 12 , wherein the therapeutic agent is selected from the group consisting of chemotherapeutics, anti-inflammatories, fatty acids, antibiotics, antivirals, small molecules, siRNA, and DNA.
19. The method of claim 12 , wherein the multicompartment delivery system further comprises a second therapeutic agent selected from the group consisting of chemotherapeutics, antiinflammatories, fatty acids, antibiotics, antivirals, small molecules, siRNA, and DNA.
20. The method of claim 19 , wherein the outer hydrophobic compartment encapsulates the second therapeutic agent.
21. The method of claim 19 , wherein the nanoparticle consists of a polymeric matrix, an imaging agent, and two therapeutic agents.
22. The method of any one of claims 12 , 13 , or 14 - 21 , wherein the polymeric matrix comprises poly(epsilon-caprolactone), gelatin, or alginate.
23. The method of any one of claims 12 , 13 , or 14 - 21 , wherein the polymeric matrix is hydrophilic.
24. The method of claim 12 , wherein the oil is safflower oil.
25. The method of claim 12 , wherein the therapeutic agent is a gene construct.
26. The method of claim 25 wherein the gene construct is expressed in the macrophage.
27. The method of claim 25 , wherein the gene construct encodes IL-10.
28. The method of claim 25 , wherein the gene construct causes apoptosis in the macrophage.
29. The method of claim 25 , wherein the gene construct is siRNA.