Microencapsulation with polymers

• US 4,803,168 A
• Filed: 06/04/1986
• Issued: 02/07/1989
• Est. Priority Date: 09/01/1983
• Status: Expired due to Fees

• Current Assignee: Repligen Corporation
• Original Assignee: Damon Biotech, Inc. (Abbott Laboratories)
• Inventors: Jarvis, Allan P. Jr.
• Primary Examiner(s): Rosen, Sam
• Application Number:
  US06/873,283
• Time in Patent Office: 979 Days
• Field of Search: 424/31, 424/32, 424/34, 424/35, 424/94, 424/101, 424/106, 424/110, 424/DIG. 7, 435/1, 435/174, 435/175, 435/177, 435/178, 435/182, 435/188, 435/240, 435/240.22, 264/4, 3/1, 935/54
• US Class Current: 435/357
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• 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: B01J 13/08 Simple coacervation, i.e. addition of highly hydrophilic material combined with spraying B01J13/043; combined with mechanical division B01J13/04
• CPC Class Codes: B01J 13/20 After-treatment of capsule walls, e.g. hardening
• CPC Class Codes: C12N 11/04 entrapped within the carrier, e.g. gel or hollow fibres
• CPC Class Codes: C12N 15/02 Preparation of hybrid cells by fusion of two or more cells, e.g. protoplast fusion monoclonal antibodies C07K16/00; apparatus for cell fusion C12M

Abstract

Disclosed is a process for damage-free encapsulation of a variety of core materials including viable cells. The core material is suspended in an aqueous solution of a polymeric material containing cationic groups such as an aminated glucopolysaccharide, e.g. chitosan. A temporary matrix is formed by gelling droplets of the suspension with a divalent or multivalent anion. The temporary matrix is permanently cross-linked with a polymeric material containing plural anionic groups, e.g., polyaspartic or polyglutamic acid, to form a semipermeable membrane. The interior of the microcapsule may be resolublized by subjecting the capsule to a solution of low molecular weight cations. The process produces microcapsules which are not sticky, do not clump and allow viable cell growth and proliferation.

Claims

1. A viable cell-containing capsule comprising a semipermeable membrane defining an enclosed intracapsular volume in which viable mammalian cells are disposed within a culture medium, said membrane consisting essentially of an inner layer comprising chitosan and an outer layer comprising a polyanionic polymer, said chitosan layer and polyanionic polymer being cross-linked by ionic interaction between cationic amine groups on said chitosan and anionic groups on said polyanionic polymer to form a water-insoluble permanent capsule, said encapsulated viable cells being capable of growth and reproduction within said capsule.

2. The capsule of claim 1 wherein said polyanionic polymer is a polycarboxylated polymer.

3. The capsule of claim 2 wherein said polyanionic polymer is polyaspartic acid or a salt thereof.

4. The capsule of claim 2 wherein said polyanionic polymer is polyglutamic acid or a salt thereof.

5. The capsule of claim 1 wherein said chitosan layer and said polyanionic polymer are physiologically compatible with said cell.

6. The capsule of claim 1 wherein said cell comprises a genetically modified cell.