Hyperbranched polyglycerol-coated particles and methods of making and using thereof

Patent metadata

Field	Value
Publication number	US-12233140-B2
Application number	US-202318514738-A
Country	US
Kind code	B2
Filing date	Nov 20, 2023
Priority date	May 9, 2014
Publication date	Feb 25, 2025
Grant date	Feb 25, 2025

Abstract

Core-shell particles and methods of making and using thereof are described herein. The core is formed of or contains one or more hydrophobic materials or more hydrophobic materials. The shell is formed of or contains hyperbranched polyglycerol (HPG). The HPG coating can be modified to adjust the properties of the particles. Unmodified HPG coatings impart stealth properties to the particles which resist non-specific protein absorption and increase circulation in the blood. The hydroxyl groups on the HPG coating can be chemically modified to form functional groups that react with functional groups and adhere the particles to tissue, cells, or extracellular materials, such as proteins.

First claim

We claim:

1. Particles comprising:
(a) a core comprising one or more polymers;
(b) a shell comprising hyperbranched polyglycerol; and
(c) one or more nucleic acids, one or more peptides, or a combination thereof;
wherein the one or more polymers are more hydrophobic than the hyperbranched polyglycerol;
wherein the hyperbranched polyglycerol is covalently bound to the one or more polymers;
wherein the hyperbranched polyglycerol at the surface of the particles comprises hydroxyl groups converted to one or more reactive functional groups selected from the group consisting of aldehydes, amines, oximes, and O-substituted oximes; and
optionally wherein the particles are modified by attachment of polyethylene glycol to the surface of the particles.

2. The particles of claim 1 , wherein the polymer is biodegradable.

3. The particles of claim 2 , wherein the biodegradable polymer is an aliphatic polyester.

4. The particles of claim 3 , wherein the aliphatic polyester is selected from the group consisting of poly (lactic acid), poly (glycolic acid), and copolymers thereof.

5. The particles of claim 4 , wherein the aliphatic polyester is poly (lactic acid).

6. The particles of claim 1 , wherein the one or more reactive functional groups are aldehydes.

7. The particles of claim 1 , wherein the one or more nucleic acids, one or more peptides, or a combination thereof are dispersed within the core.

8. The particles of claim 1 , wherein the one or more nucleic acids, one or more peptides, or a combination thereof are associated with the surface of the particles.

9. The particles of claim 1 , wherein the one or more nucleic acids, one or more peptides, or a combination thereof are dispersed within the core and associated with the surface of the particles.

10. The particles of claim 1 , wherein the average diameter of the particles is from about 1 nm to about 1 mm.

11. The particles of claim 1 , wherein the one or more nucleic acids comprise one or more synthetic nucleic acids.

12. The particles of claim 1 , further comprising polyethylene glycol, wherein the polyethylene glycol is associated with the hyperbranched polyglycerol at the surface of the particles.

13. The particles of claim 12 , wherein the polyethylene glycol is covalently attached to the hyperbranched polyglycerol at the surface of the particles.

14. A pharmaceutical composition comprising the particles of claim 1 and one or more pharmaceutically acceptable carriers.

15. The pharmaceutical composition of claim 14 , wherein the one or more carriers are suitable for parenteral administration, or enteral administration, or topical administration.

16. The pharmaceutical composition of claim 14 , wherein the one or more pharmaceutically acceptable carriers comprise one or more water soluble polymers.

17. The pharmaceutical composition of claim 16 , wherein the one or more water soluble polymers are selected from the group consisting of polyvinylpyrrolidone, dextran, carboxymethylcellulose, and polyethylene glycol.

18. The pharmaceutical composition of claim 16 , wherein the one or more water soluble polymers comprise polyethylene glycol.

19. The pharmaceutical composition of claim 14 , wherein the one or more pharmaceutically acceptable carriers are associated with the surface of the shell of the particles.

Assignees

• Univ Yale

Inventors

• Deng Yang
• Ediriwickrema Asiri
• Saltzman W Mark

Classifications

• A61Q17/04

  Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations · CPC title

• A61K2800/624

  by macromolecular compounds · CPC title

• A61K2800/413

  Nanosized, i.e. having sizes below 100 nm · CPC title

• A61K2800/412

  Microsized, i.e. having sizes between 0.1 and 100 microns · CPC title

• A61K8/90

  Block copolymers (A61K8/89 takes precedence) · CPC title