Methods for inducing macrophage conversion in a wound

Patent metadata

Field	Value
Publication number	US-11083818-B2
Application number	US-201816157760-A
Country	US
Kind code	B2
Filing date	Oct 11, 2018
Priority date	Nov 20, 2013
Publication date	Aug 10, 2021
Grant date	Aug 10, 2021

Abstract

One aspect of the invention provides a method of sequentially inducing macrophage conversion in a wound. The method includes: (a) administering IL-4 to induce conversion of a first population of wound macrophages in the wound to M2A macrophages; and then (b) administering IL-10, dexamethasone, or a dexamethasone analog to induce conversion of a second population of wound macrophages in the wound to M2C macrophages.

First claim

The invention claimed is:

1. A method of sequentially inducing macrophage conversion in a wound, the method comprising:
(a) sequentially administering IL-4 to induce conversion of a first population of wound macrophages in the wound to M2A macrophages; and then
(b) sequentially administering IL-10, dexamethasone, or a dexamethasone analog to induce conversion of a second population of wound macrophages in the wound to M2C macrophages;
wherein steps (a) and (b) are sequentially performed by a delivery system; and
wherein the delivery system is a sequential controlled-release delivery system.

2. The method of claim 1 , wherein the sequential controlled-release delivery system comprises IL-4 bound to the delivery system through a binding molecule.

3. The method of claim 2 , wherein the binding molecule is non-covalently bound to the delivery system.

4. The method of claim 2 , wherein the IL-4 is covalently bound to an affinity molecule that interacts with the binding molecule.

5. The method of claim 2 , wherein the IL-4 is released by dissociating the IL-4 from the binding molecule.

6. The method of claim 1 , wherein the sequential controlled-release delivery system comprises IL-10 bound to the delivery system through a binding molecule.

7. The method of claim 6 , wherein the IL-10 is bound to an affinity molecule that interacts with the binding molecule, wherein the binding molecule is bound to the delivery system.

8. The method of claim 6 , wherein the affinity molecule is non-covalently bound to the delivery system.

9. The method of claim 6 , wherein the bound IL-10 is released by enzymatic cleavage by an enzyme that is present in the wound.

10. The method of claim 9 , wherein the enzyme comprises a matrix metalloprotease that cleaves the bound IL-10 from the delivery system.

11. The method of claim 1 , wherein the sequential controlled-release drug delivery system is an affinity-based delivery system.

12. The method of claim 1 , wherein sequentially inducing macrophage conversion in the wound promotes tissue remodeling.

13. The method of claim 1 , wherein when the macrophage conversion in the wound occurs, the wound is treated.

14. The method of claim 1 , wherein the wound is a chronic wound.

Assignees

• Univ Drexel

Inventors

• Spiller Kara L
• Nassiri Sina

Classifications

• C08L89/00

  Compositions of proteins; Compositions of derivatives thereof (foodstuff preparations A23J3/00) · CPC title

• C08L5/08

  Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof · CPC title

• A61L26/0066 Primary

  Medicaments; Biocides · CPC title

• A61K38/2066

  IL-10 · CPC title

• A61L27/20

  Polysaccharides · CPC title