Biocompatible microcapsules

• US 5,820,882 A
• Filed: 11/10/1994
• Issued: 10/13/1998
• Est. Priority Date: 10/15/1990
• Status: Expired due to Term

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Sawhney, Amarpreet S., Hubbell, Jeffrey A.
• Primary Examiner(s): Spear, James M.
• Application Number:
  US08/336,393
• Time in Patent Office: 1,433 Days
• Field of Search: 424/497, 424/490, 424/462, 424/482, 424/423, 424/424, 424/493, 424/491, 424/460, 424/461
• US Class Current: 424/491
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61K 47/645 Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
• CPC Class Codes: A61K 47/6925 the form being a microcapsule, nanocapsule, microbubble or nanobubble
• 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)
• CPC Class Codes: A61K 9/5073 having two or more different coatings optionally including drug-containing subcoatings

Abstract

Biocompatible microcapsules useful for transplanting foreign material into an animal body, and the method of their production, are described, wherein the microcapsules contain an outermost layer of water soluble non-ionic polymers such as PEO to create resistance to cell adhesion on the surface of the microcapsules.

Claims

1. A biocompatible microcapsule for transplantation into an animal comprising a membrane of more than one layer, with an outermost layer of hydrophilic non-ionic water soluble polymers that have been covalently grafted to at least one of the layers, made of polyamine, polyamide or polyimine polycationic polymers able to form strong membrane coacervates of the microcapsule membrane, wherein the hydrophilic polymer is of an effective molecular weight to shield the microcapsules from cellular adhesion and provide an effective permeability to the microcapsules.

2. The microcapsule of claim 1 wherein the non-ionic water soluble polymers are selected from the group consisting of poly(ethylene oxide), poly(vinyl pyrrolidone), poly(ethyl oxazoline), poly(vinyl alcohol) and polysaccharides.

5. The microcapsule of claim 2 wherein the water soluble non-ionic polymers are branched.

6. The microcapsule of claim 2 wherein the water soluble non-ionic polymers are unbranched.

7. The microcapsule of claim 1 wherein the polycationic polymers are selected from the group consisting of polylysine, polyornithine, polyethyleneimine, polyallylamine, and mixed copolymers thereof.

3. A biocompatible microcapsule for transplantation into an animal comprising a membrane of more than one layer, with an outermost layer of dextran that has been covalently grafted to at least one of the layers, made of polyamine, polyamide or polyimine polycationic polymers able to form strong membrane coacervates of the microcapsule membrane wherein the dextran is of an effective molecular weight to shield the microcapsules from cellular adhesion and provide an effective permeability to the microcapsules.

4. A biocompatible microcapsule for transplantation into an animal comprising a membrane of more than one layer, with an outermost layer of hyaluronic acid that has been covalently grafted to at least one of the layers, made of polyamine, polyamide or polyimine polycationic polymers able to form strong membrane coacervates of the microcapsule membrane, wherein the hyaluronic acid is of an effective molecular weight to shield the microcapsules from cellular adhesion and provide an effective permeability to the microcapsules.

8. A biocompatible microcapsule for transplantations into an animal comprising a membrane of more than one layer, with an outermost layer of hydrophilic non-ionic water soluble polymers selected from the group consisting of poly(ethylene oxide), poly(vinyl pyrrolidone), poly(ethyl oxazoline), poly(vinyl alcohol) and polysaccharides, or copolymers thereof, that have been covalently grafted to at least one of the other layers, made of polyamine, polyamide or polyimine polycationic polymers selected from the group consisting of polycationic polyamino acids, polyethyleneimine and polyallylamine, or copolymers thereof, of the microcapsule membrane, wherein the hydrophilic polymer is of an effective molecular weight to shield the microcapsules from cellular adhesion and provide an effective permeability to the microcapsules.

9. The microcapsule of claim 8 wherein the polycationic polyamino acids are selected from the group consisting of polylysine, polyornithine, and copolymers thereof.

10. An improved biocompatible microcapsule for transplantation into an animal, having improved resistance to overgrowth by cells, comprising a membrane of more than one layer, characterized in that the outermost layer comprises exposed non-ionic chains of a graft copolymer, the graft copolymer comprising at least one block of a polycationic polymer and at least one block of a hydrophilic, water soluble, non-ionic polymer, and the graft copolymer adhered to the microcapsule predominantly by ionic bonds, wherein the hydrophilic polymer is of an effective molecular weight to shield the microcapsules from cellular adhesion and provide an effective permeability to the microcapsules.