# US 2009/0214662 A1 · Surface-layer protein coated microspheres and uses thereof

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- Number: US 2009/0214662 A1
- Document ID: US20090214662A1
- Status: Published application
- Kind: A1
- Application number: 12/162,011
- Filed: 2007-01-24
- Published: 2009-08-27
- Earliest claimed: 2006-01-24
- Assignees: University of Maryland, Baltimore
- Inventors: Erik P.H. de Leeuw; Wuyuan Lu
- Web page: https://patentgrep.com/patent/US20090214662A1

## CPC

- A61K 31/138: Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine (atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377)
- A61K 9/5052: {Proteins, e.g. albumin}
- A61K 38/164: {from bacteria}
- A61K 38/1729: {Cationic antimicrobial peptides, e.g. defensins}
- A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone}
- A61K 47/34: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence)
- A61K 9/5068: {Cell membranes or bacterial membranes enclosing drugs (liposomes with additional exogenous lipids A61K9/127)}
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The invention provides surface-layer protein coated microspheres for delivery of a therapeutic agent to the intestine. These surface-layer protein coated microspheres generally include a core encapsulated by a microsphere which is coated by surface layer protein. The core includes a therapeutic agent, such as a defensin. The invention also includes methods of making and using the surface-layer protein coated microspheres of the invention for administering therapeutic agents to a subject in need thereof. The invention also includes pharmaceutical dosage units that include the surface-layer protein coated microspheres of the invention. The invention further includes various labeled defensins for use in the study of the properties and actions of defensins, and further includes the use of defensins, particularly HD5α in the treatment of inflammatory conditions of the bowel, such as Crohn's disease.

## Claims

### Claim 1

A delivery device for administering a therapeutic agent to a specific tissue comprising:
a therapeutic agent encapsulated in a microsphere, and
surface layer proteins coating at least a section of the microsphere, wherein said surface layer proteins are self-assembling proteins involved in bacterial-host adhesion and wherein the surface-layer protein has affinity for the specific tissue.

### Claim 2 (depends on 1)

The delivery device of claim 1, wherein the specific tissue is intestinal epithelium.

### Claim 3 (depends on 1)

The delivery device of claim 1, wherein the surface-layer protein is SlpA purified from Lactobacillus brevis.

### Claim 4 (depends on 1)

The delivery device of claim 1, wherein the therapeutic agent is a native defensin or an analog thereof.

### Claim 5 (depends on 1)

The delivery device of claim 1 wherein the therapeutic agent is HD5α or an analog thereof.

### Claim 6 (depends on 1)

The deliver device of claim 1 wherein the microsphere is fabricated of or comprises a polymeric substance selected from the group consisting of polyorthoesters, polyanhydrides, polyamides, polyalkylcyanoacrylates, polyesters, polyphosphazines, pseudo-polyamino acids, proteins, and polysaccharides.

### Claim 7 (depends on 1)

The delivery device of claim 1, wherein the microsphere comprises poly(DL-lactide-co-glycolide).

### Claim 8 (depends on 1)

The delivery device of claim 1 wherein the surface layer protein is from a Lactobacillus sp.

### Claim 9 (depends on 1)

The delivery device of claim 1, wherein the surface layer protein has affinity for an extracellular membrane component.

### Claim 10 (depends on 3)

The delivery device of claim 3, wherein the surface layer protein has affinity for fibronectin.

### Claim 11 (depends on 1)

The delivery device of claim 1, wherein the surface layer protein has affinity for at least two extracellular matrix components selected from fibronectin, laminin, fibrinogen and collagen.

### Claim 12 (depends on 1)

The delivery device of claim 1, wherein the therapeutic agent is HD5α or analog thereof, and the surface layer protein is SlpA from Lactobacillus brevis.

### Claim 13 (depends on 1)

The delivery device of claim 1 in a pharmaceutically acceptable carrier.

### Claim 14 (depends on 12)

The delivery device of claim 12 in a pharmaceutically acceptable carrier.

### Claim 15 (depends on 14)

The delivery device claim 14 is provided in the form of a unitary dosage unit.

### Claim at position 16

-17. (canceled)

### Claim 18

A method of preparing a delivery device for specific tissue, the method comprising:
encapsulating a therapeutic agent in a microsphere, and
coating at least a section of the microsphere with surface layer proteins, wherein said surface layer proteins are self-assembling proteins involved in bacterial-host adhesion and wherein the surface-layer protein has affinity for the specific tissue.

### Claim 19 (depends on 18)

The method of claim 18, wherein the specific tissue is intestinal epithelium.

### Claim 20 (depends on 18)

The method of claim 18, wherein the surface-layer protein is SlpA purified from Lactobacillus brevis.

### Claim 21 (depends on 18)

The method of claim 18, wherein the therapeutic agent is a native defensin or an analog thereof.

### Claim 22 (depends on 18)

The method of claim 18, wherein the therapeutic agent is HD5α or an analog thereof.

### Claim 23 (depends on 18)

The method of claim 18, wherein the microsphere is fabricated of or comprises a polymeric substance selected from the group consisting of polyorthoesters, polyanhydrides, polyamides, polyalkylcyanoacrylates, polyesters, polyphosphazines, pseudo-polyamino acids, proteins, and polysaccharides.

### Claim 24 (depends on 18)

The method of claim 18, wherein the microsphere comprises poly(DL-lactide-co-glycolide).

### Claim 25 (depends on 18)

The method of claim 18, wherein the surface layer protein is from a Lactobacillus sp.

### Claim 26 (depends on 18)

The method of claim 18, wherein the surface layer protein has affinity for an extracellular membrane component.

### Claim 27 (depends on 18)

The method of claim 18, wherein the surface layer protein has affinity for at least one extracellular matrix components selected from fibronectin, laminin, fibrinogen and collagen.

### Claim 28 (depends on 18)

The method of claim 18, wherein the therapeutic agent is HD5α or analog thereof, and the surface layer protein is SlpA from Lactobacillus brevis.

### Claim 29 (depends on 1)

A method of treating a disease condition affecting the small and/or large intestine comprising administering to a subject a pharmaceutical formulation comprising surface-layer protein coated microspheres of claim 1.

### Claim 30 (depends on 29)

The method of claim 29 wherein the disease condition comprises Crohn's disease.

### Claim at position 30

31-35. (canceled)