Cross-linked alginate-polyalkylene glycol polymer coatings for encapsulation and methods of making the same

• US 8,728,520 B2
• Filed: 12/08/2009
• Issued: 05/20/2014
• Est. Priority Date: 12/08/2008
• Status: Active Grant

• Current Assignee: University of Miami
• Original Assignee: University of Miami
• Inventors: Stabler, Cherie, Gattas-Asfura, Kerim, Finn, Kristina, Ricordi, Camillo, Rengifo, Hernan R
• Primary Examiner(s): Justice, Gina C
• Application Number:
  US12/633,270
• Publication Number:
  US 20100143464A1
• Time in Patent Office: 1,624 Days
• Field of Search: 424/463
• US Class Current: 424/463
• CPC Class Codes: A61K 9/5031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)

Abstract

A biocompatible capsule comprising a biological material encapsulated by a covalently stabilized coating and a method of making the same are disclosed. The biological material can be a material selected from the group consisting of cells, such as islets of Langerhans, pharmaceuticals, and biological agents. The coating can be formed by reacting an alginate-[polyalkylene glycol (PAG)-X¹]_n, and a multi-functional PAG-X², to form covalent bonds, wherein n is an integer greater than 0, a first one of X¹ and X² is N₃, and a second one of X¹ and X² is selected from the group consisting of:

wherein R¹=CH₃, CH₂CH₃, CH(CH₃)₂,

• • R²=N(CH₃)₂, OCH₃, OH, CH₃, H, F, Cl, Br or NO₂, and
  • R³=OCH₃, CH₃, H, F, Cl or NO₂.

Claims

1. A biocompatible capsule, comprising:

a biological material; and

a covalently stabilized coating encapsulating said biological material, said covalently stabilized coating formed by reacting

(i) alginate-[polyalkylene glycol (PAG)-X¹]_n, and

(ii) multi-functional PAG-X², to form covalent bonds, wherein n is 15, a first one of X¹ and X² is N₃, and a second one of X¹ and X² is

2. The biocompatible capsule according to claim 1, wherein the biological material comprises a material selected from the group consisting of cells, pharmaceuticals, biological agents, biopolymers, RNA, DNA and fragments of DNA or RNA.

3. The biocompatible capsule according to claim 1, wherein said biological material comprises islets of Langerhans.

4. The biocompatible capsule according to claim 1, wherein said covalently stabilized coating comprises a plurality of monolayers.

5. The biocompatible capsule according to claim 3, wherein said plurality of monolayers alternate between monolayers of Alginate-[PAG-X¹]_n reaction products and monolayers of multi-functional PAG-X² reaction products.

6. The biocompatible capsule according to claim 1, wherein said multi-functional PAG-X² comprises a multi-arm PAG-X² having at least three PAG-X² arms.

7. The biocompatible capsule according to claim 1, wherein said alginate-[polyethylene glycol (PAG)-X²]_n molecule or said multi-functional PAG-X² molecule further comprise an additional terminal ligand, X³, wherein X³ is selected from the group consisting of proteins, imaging labels, nanoparticles, biopolymers, RNA, DNA, and fragments of RNA or DNA.

8. The biocompatible capsule according to claim 1, wherein said covalently stabilized coating is covalently bonded to said biological material.

9. The biocompatible capsule according to claim 8, wherein said coating is covalently bonded to said biological material by reacting a first terminal ligand of compound (A) with amino groups on a surface of said biological material, wherein compound (A) comprises:

said first terminal ligand comprising