Living cells microencapsulated in a polymeric membrane having two layers

• US 5,620,883 A
• Filed: 04/01/1994
• Issued: 04/15/1997
• Est. Priority Date: 04/01/1994
• Status: Expired due to Term

• Current Assignee: Johns Hopkins University
• Original Assignee: Johns Hopkins University
• Inventors: Shao, Wen, Leong, Kam W.
• Primary Examiner(s): Naff, David M.
• Assistant Examiner(s): WARE, DEBORAH K
• Application Number:
  US08/221,627
• Time in Patent Office: 1,110 Days
• Field of Search: 435/174, 435/177, 435/178, 435/182, 264/4.32, 424/93 R, 424/408, 424/459, 424/460, 424/462, 424/491, 424/497, 424/93.1, 514/963, 514/970
• US Class Current: 435/174
• CPC Class Codes: A61K 9/1658 Proteins, e.g. albumin, gelatin
• CPC Class Codes: A61K 9/5073 having two or more different coatings optionally including drug-containing subcoatings
• CPC Class Codes: C12N 11/02 Enzymes or microbial cells immobilised on or in an organic carrier

Abstract

A biocompatible microcapsule containing living cells encapsulated in a membrane is disclosed. The membrane is a complex formed by the cohesion of two polymer layers. An inner layer comprises a substrate biopolymer and an outer layer comprises a synthetic polyelectrolyte having an electrolytic charge opposite that of the substrate biopolymer. Droplets of a solution of substrate biopolymer containing a suspension of living cells can be added to a solution comprising the synthetic polyelectrolyte to form the encapsulates. The membrane is formed by the cohesion of the oppositely-charge polymer layers to form a complex of substrate biopolymer and synthetic polyelectrolyte. Preferably, the inner layer contains a cationic biopolymer, such as collagen modified to have a pKI of 9, or an anionic biopolymer such as esterified or modified hyaluronic acid. Further, the membrane is permeable to materials which are able to maintain normal metabolic functions of bioactive cells which are encapsulated in the inner layer of the membrane. In addition the membrane is permeable to products released by the bioactive cells and impermeable to agents of the immune system which are responsible for immunological reactions that result in an immune rejection of bioactive cells and products thereof.

Claims

1. A biocompatible microcapsule suitable for introduction into a host, said microcapsule comprising:

(a) bioactive cells enclosed within a membrane,

(b) said membrane comprising an inner layer and an outer layer, said inner layer comprising a cationic biopolymer consisting of collagen modified to have a pKI of at least about 9 or an anionic biopolymer selected from the group consisting of esterified hyaluronic acid and amine modified hyaluronic the cells and supporting acid and said inner layer containing the cells and supporting maintenance of cell function, said outer layer comprising a biocompatible synthetic polyelectrolyte having an electrolytic charge opposite to that of the inner layer, said inner and outer layer having charges sufficient to form a complex of said biopolymer and said polyelectrolyte when a solution of the biopolymer containing a suspension of the bioactive cells is introduced into a solution of the synthetic polyelectrolyte,

(c) said membrane being permeable to materials necessary to sustain the normal metabolic functions of the bioactive cells and to products released by the bioactive cells and impermeable to immune system components responsible for immunological reactions that result in immune rejection of the bioactive cells by the host.

2. The biocompatible microcapsule of claim 1, wherein the bioactive cells are attachment-dependent.

3. The biocompatible microcapsule of claim 1, wherein the bioactive cells are attachment-independent.

4. The biocompatible microcapsule of claim 1, wherein the synthetic polyelectrolyte is an acrylate copolymer or terpolymer containing (a) at least one of acrylic acid and methacrylic acid and (b) at least one of hydroxyethyl methacrylate and hydroxylproply methacrylate.

5. The biocompatible microcapsule of claim 1 wherein the bioactive cells are selected from the group consisting of intact islets of Langerhans, alpha cells, beta cells, and mixture thereof, and the product released by the bioactive cells is insulin.