Degradable Microparticles for Protein and Small Molecule Delivery

Patent metadata

Field	Value
Publication number	US-2018133148-A1
Application number	US-201715782388-A
Country	US
Kind code	A1
Filing date	Oct 12, 2017
Priority date	Oct 14, 2016
Publication date	May 17, 2018
Grant date	—

Abstract

The invention relates to a microparticle platform and pharmaceutical compositions capable of recruiting pro-regenerative cells to and/or reducing inflammation at the site of muscle, joint, tendon, and/or ligament damage. The invention further relates to methods of treating muscle, joint, tendon, and/or ligament damage comprising administering the microparticles or pharmaceutical compositions comprising the microparticles.

First claim

What is claimed is:

1 . A degradable microparticle comprising a GAG-based body and an active agent selected from a protein and a small molecule, wherein the active agent is positively charged.

2 . The degradable microparticle of claim 1 , wherein the GAG-based body is an N-desulfated heparin-based body.

3 . The degradable microparticle of claim 1 , wherein the degradable microparticle further comprises DTT or a poly (ethylene glycol)-based linker.

4 . The degradable microparticle of claim 3 , wherein the poly (ethylene glycol)-based linker is a PEGDA-based linker.

5 . The degradable microparticle of claim 1 , wherein the active agent is a protein.

6 . The degradable microparticle of claim 5 , wherein the active agent is SDF-1α or TSG-6.

7 . The degradable microparticle of claim 1 , wherein the active agent is a small molecule.

8 . The degradable microparticle of claim 1 , wherein the degradable microparticle is between about 30 and about 80 micrometers in diameter.

9 . The degradable microparticle of claim 1 , wherein the GAG-based body is an N-desulfated heparin-based body, the degradable microparticle further comprises DTT and a PEGDA-based linker, the active agent is selected from SDF-1α, TSG-6, FTY720 and combinations thereof, and wherein the degradable microparticle is between about 30 and about 80 micrometers in diameter.

10 . A pharmaceutical composition comprising a plurality of the degradable microparticles of claim 1 and a pharmaceutically acceptable carrier, additive, or excipient, wherein the pharmaceutical composition is in a liquid injectable dosage form.

11 . A method of fabricating a degradable Hep microparticle comprising adding PEGDA and dithiothreitol (DTT) to a solution comprising bovine serum albumin (BSA) in PBS, incubating at 30-40° C. for 20-40 minutes, adding Hep −N MAm to the solution, and incubating the aqueous phase for 20-40 minutes.

12 . A method of recruiting pro-regenerative cells to a site of muscle, joint, tendon, or ligament damage, the method comprising introducing into the site of muscle, joint, tendon, or ligament damage a degradable microparticle comprising a GAG-based body and an amount of an active agent selected from a protein and a small molecule effective to recruit pro-regenerative cells to the site of muscle, joint, tendon, or ligament damage.

13 . The method of claim 12 , wherein the degradable microparticle is introduced into the site of muscle, joint, tendon, or ligament damage by an intramuscular or intra-articular injection.

14 . The method of claim 12 , wherein a pharmaceutical composition comprising a plurality of the degradable microparticles and a pharmaceutically acceptable carrier, additive, or excipient is introduced into the site of muscle, joint, tendon, or ligament damage by injection.

15 . The method of claim 12 , wherein the active agent is SDF-1α.

16 . The method of claim 12 , wherein the muscle damage is rotator cuff damage.

17 . The method of claim 12 , wherein the degradable microparticle is between about 30 and about 80 micrometers in diameter.

18 . A method of reducing inflammation at a site of muscle, joint, tendon, or ligament damage, the method comprising introducing into the site of muscle, joint, tendon, or ligament damage a degradable microparticle comprising a GAG-based body and an amount of an active agent selected from a protein and a small molecule effective to reduce inflammation at the site of muscle, joint, tendon, or ligament damage.

19 . The method of claim 18 , wherein the joint damage is osteoarthritis and the active agent is TSG-6.

20 . The method of claim 18 , wherein the degradable microparticle is between about 30 and about 80 micrometers in diameter.

Assignees

• Georgia Tech Res Inst

Inventors

• Tellier Liane Elizabeth
• Botchwey Edward
• Falis Alexandra Ann
• Temenoff Johnna Sue

Classifications

• A61K9/0024 Primary

  Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue (compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L) · CPC title

• A61K38/191

  Tumor necrosis factors [TNF], e.g. lymphotoxin [LT], i.e. TNF-beta · CPC title

• A61P19/04

  for non-specific disorders of the connective tissue · CPC title

• A61P21/00

  Drugs for disorders of the muscular or neuromuscular system · CPC title

• A61K38/195

  Chemokines, e.g. RANTES · CPC title