# US 12,178,849 B2 · Autoimmune disease treatment with chemokine-loaded alginate microparticles

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- Number: US 12,178,849 B2
- Document ID: US12178849B2
- Status: Granted
- Kind: B2
- Application number: 17/460,867
- Filed: 2021-08-30
- Published: 2021-12-16
- Granted: 2024-12-31
- Earliest claimed: 2012-08-03
- Assignees: University of Pittsburgh—Of the Commonwealth System of Higher Education; Ri.MED Foundation
- Applicants: University of Pittsburgh—of the Commonwealth System of Higher Education; Ri.MED Foundation
- Inventors: Steven R. Little; Riccardo Gottardi; Mintai Peter Hwang; Daniel DeSantis
- Web page: https://patentgrep.com/patent/US12178849B2

## CPC

- A61K 38/1858: {Platelet-derived growth factor [PDGF]}
- A61K 9/1271: Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911})
- A61K 9/5036: {Polysaccharides, e.g. gums, alginate; Cyclodextrin}
- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- A61K 38/1841: {Transforming growth factor [TGF]}
- A61K 38/19: Cytokines; Lymphokines; Interferons
- A61K 38/30: Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2 {(insulin-like growth factor binding protein A61K38/1754)}
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- 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

## Abstract

The present invention provides microparticles that induce the migration of multipotent stem cells to the anatomical site of the microparticles. Various release profiles are demonstrated that depend upon the relative concentration of alginate in the chemokine-loaded microparticle. Local administration and/or intraarticular injection of the microparticles are useful in conditions such as osteoarthritis. Targeted systemic delivery of the alginate chemokine microparticles to distant anatomical sites subjected to autoimmune disease symptomology can be performed by encapsulation within liposomes having targeting ligands. Consequently, upon the creation of the appropriate chemokine gradient, multipotent stem cells will migrate to the distant anatomical site where the liposomes are attached.

## Claims

### Claim 1

A controlled release microparticle comprising
a) a chemokine;
b) alginate at a concentration from about 1% to about 4% v of alginate/v of the microparticle, and
c) hypromellose (HPMC).

### Claim 2 (depends on 1)

The microparticle of claim 1, wherein the chemokine is selected from the group consisting of transforming growth factor-alpha (TGFα), insulin-like growth factor 1 (IGF-1), insulin-like growth factor 2 (IGF-2), CXC motif chemokine 12 (CXCL12), C—C motif chemokine ligand 5 (CCL5), and C—C motif chemokine 22 (CCL22).

### Claim 3 (depends on 1)

The microparticle of claim 1, wherein the alginate microparticle is biodegradable.

### Claim 4 (depends on 1)

The microparticle of claim 1, wherein the chemokine is released to form a biomimetic gradient.

### Claim 5

A method of treating an autoimmune disease in a subject in need thereof, comprising administering a controlled release microparticle comprising:
a) a chemokine;
b) alginate at a concentration from about 1% to about 4% v of alginate/v of the microparticle, and
c) hypromellose (HPMC).

### Claim 6 (depends on 5)

The method of claim 5, wherein the chemokine is selected from the group consisting of transforming growth factor-alpha (TGFα), insulin-like growth factor 1 (IGF-1), insulin-like growth factor 2 (IGF-2), CXC motif chemokine 12 (CXCL12), C—C motif chemokine ligand 5 (CCL5), and C—C motif chemokine 22 (CCL22).

### Claim 7 (depends on 5)

The method of claim 5, wherein the chemokine induces migration of multipotent stem cells towards the microparticle.

### Claim 8 (depends on 5)

The method of claim 5, wherein the chemokine is released from the microparticle to form a biomimetic gradient.

### Claim 9 (depends on 5)

The method of claim 5, wherein the microparticle is encapsulated in a liposome.

### Claim 10 (depends on 5)

The method of claim 5, wherein the administering is parental, topical, oral, or intracranial.

### Claim 11 (depends on 5)

The method of claim 5, wherein the autoimmune disease is selected from the group consisting of type 1 diabetes, alopecia areata, systemic lupus erythematosus, Sjogren syndrome, rheumatoid arthritis, antiphospholipid antibody syndrome, multiple sclerosis, Crohn's disease, ulcerative colitis, and dermatomyositis.

### Claim 12 (depends on 5)

The method of claim 5, wherein the subject is human.