# US 10,500,156 B2 · Multi-compartmental macrophage delivery

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- Number: US 10,500,156 B2
- Document ID: US10500156B2
- Status: Granted
- Kind: B2
- Application number: 13/636,900
- Filed: 2011-03-24
- Published: 2013-09-19
- Granted: 2019-12-10
- Earliest claimed: 2010-03-24
- Assignees: Northeastern University
- Applicants: Mansoor M. Amiji; Mayur Kalariya; Shardool Jain; Husain Attarwala
- Inventors: Mansoor M. Amiji; Mayur Kalariya; Shardool Jain; Husain Attarwala
- Web page: https://patentgrep.com/patent/US10500156B2

## CPC

- A61K 9/113: Multiple emulsions, e.g. oil-in-water-in-oil {(A61K9/0026 takes precedence)}
- A61K 9/145: {with organic compounds}
- A61K 9/5031: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)}
- A61K 9/5161: {Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin}
- A61K 38/191: {Tumor necrosis factors [TNF], e.g. lymphotoxin [LT], i.e. TNF-beta}
- A61K 38/217: {IFN-gamma}
- A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants
- A61K 47/6925: {the form being a microcapsule, nanocapsule, microbubble or nanobubble}
- A61K 47/6935: {the polymer being obtained otherwise than by reactions involving carbon to carbon unsaturated bonds, e.g. polyesters, polyamides or polyglycerol}
- A61K 49/0041: {Xanthene dyes, used in vivo, e.g. administered to a mice, e.g. rhodamines, rose Bengal (in vivo G01N)}
- A61K 49/0047: {Green fluorescent protein [GFP]}
- A61K 49/0054: {Macromolecular compounds, i.e. oligomers, polymers, dendrimers}
- A61K 49/0076: {dispersion, suspension, e.g. particles in a liquid, colloid, emulsion}
- A61K 49/0091: {Microparticle, microcapsule, microbubble, microsphere, microbead, i.e. having a size or diameter higher or equal to 1 micrometer}
- A61K 49/0093: {Nanoparticle, nanocapsule, nanobubble, nanosphere, nanobead, i.e. having a size or diameter smaller than 1 micrometer, e.g. polymeric nanoparticle}
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- B82Y 5/00: Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
- A61K 9/5169: {Proteins, e.g. albumin, gelatin}
- A61K 2039/55555: {Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES

## Abstract

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.

## Claims

### Claim 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.

### Claim 2 (depends on 1)

The method of claim 1, wherein the imaging agent is selected from the group consisting of colloidal gold, iron-oxide crystals, and quantum dots.

### Claim 3 (depends on 1)

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.

### Claim 4 (depends on 1)

The method of claim 1, wherein the imaging agent is a fluorophore.

### Claim 5 (depends on 2, 3)

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.

### Claim 6 (depends on 1)

The method of claim 1, wherein the nanoparticle consists of a polymeric matrix and two imaging agents.

### Claim 7 (depends on 6)

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.

### Claim 8 (depends on 5)

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.

### Claim 9 (depends on 1)

The method of claim 1, wherein the polymeric matrix comprises poly(epsiloncaprolactone), gelatin, or alginate.

### Claim 10 (depends on 1)

The method of claim 1, wherein the polymeric matrix is hydrophilic.

### Claim 11 (depends on 1)

The method of claim 1, wherein the oil is safflower oil.

### Claim 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.

### Claim 13 (depends on 12)

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.

### Claim 14 (depends on 12)

The method of claim 12, wherein the nanoparticle consists of a polymeric matrix, an imaging agent, and at least one therapeutic agent.

### Claim 15 (depends on 14)

The method of claim 14, wherein the imaging agent is selected from the group consisting of colloidal gold, iron-oxide crystals, and quantum dots.

### Claim 16 (depends on 14)

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.

### Claim 17 (depends on 14)

The method of claim 14, wherein the imaging agent is a fluorophore.

### Claim 18 (depends on 12)

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.

### Claim 19 (depends on 12)

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.

### Claim 20 (depends on 19)

The method of claim 19, wherein the outer hydrophobic compartment encapsulates the second therapeutic agent.

### Claim 21 (depends on 19)

The method of claim 19, wherein the nanoparticle consists of a polymeric matrix, an imaging agent, and two therapeutic agents.

### Claim 22 (depends on 12, 13)

The method of any one of claims 12, 13, or 14-21, wherein the polymeric matrix comprises poly(epsilon-caprolactone), gelatin, or alginate.

### Claim 23 (depends on 12, 13)

The method of any one of claims 12, 13, or 14-21, wherein the polymeric matrix is hydrophilic.

### Claim 24 (depends on 12)

The method of claim 12, wherein the oil is safflower oil.

### Claim 25 (depends on 12)

The method of claim 12, wherein the therapeutic agent is a gene construct.

### Claim 26 (depends on 25)

The method of claim 25 wherein the gene construct is expressed in the macrophage.

### Claim 27 (depends on 25)

The method of claim 25, wherein the gene construct encodes IL-10.

### Claim 28 (depends on 25)

The method of claim 25, wherein the gene construct causes apoptosis in the macrophage.

### Claim 29 (depends on 25)

The method of claim 25, wherein the gene construct is siRNA.