Method of encapsulating biological substances in microspheres

• US 5,453,368 A
• Filed: 08/27/1993
• Issued: 09/26/1995
• Est. Priority Date: 08/27/1993
• Status: Expired due to Term

• Current Assignee: Brown University, Neurotech S.A. (LivaNova Plc)
• Original Assignee: Brown University
• Inventors: Tresco, Patrick A., Mills, John F.
• Primary Examiner(s): Lovering, Richard D.
• Application Number:
  US08/113,778
• Time in Patent Office: 760 Days
• Field of Search: 264/4.3, 264/4.6, 264/4, 435/178, 435/182, 424/424, 424/425, 424/493, 424/494, 424/497, 424/93.1, 514/866, 514/885, 514/962, 425/5, 935/54
• US Class Current: 435/182
• CPC Class Codes: A61K 9/5089 Processes
• CPC Class Codes: B01J 13/04 by physical processes, e.g. drying, spraying
• CPC Class Codes: B01J 13/14 Polymerisation; cross-linking
• CPC Class Codes: C12N 11/04 entrapped within the carrier, e.g. gel or hollow fibres
• CPC Class Codes: C12N 2533/30 Synthetic polymers
• CPC Class Codes: C12N 5/0012 Cell encapsulation

Abstract

A method for encapsulating a biological substance is biocompatible microcapsules is disclosed, said method comprising:

a) maintaining a coating-forming liquid film sheet comprising a solution of a soluble organic polymer in an organic solvent,

b) causing droplets comprising biological substance is an aqueous medium to pass through said sheet to form microcapsules comprising cores of said droplets coated by said liquid film, and

c) permitting said microcapsules to pass through said sheet so that a portion of said polymer precipitates in the presence of water in said droplets while evaporating a portion of said solvent to form a continuous permeable polymer coating of sufficient structural that said microcapsules are self-supporting.

Claims

1. A method for encapsulating a biological substance in biocompatible microcapsules comprising:

(a) maintaining a coating-forming liquid film sheet, said sheet comprising a solution comprising a soluble organic polymer dissolved in an organic solvent,

(b) causing droplets comprising biological substances in an aqueous medium to pass through said sheet to form microcapsules comprising cores of said droplets coated by said liquid film, and

(c) permitting said microcapsules to pass through said sheet so that a portion of said polymer precipitates in the presence of the water in said droplets while evaporating a portion of said solvent to form a continuous permeable polymer coating of sufficient structural integrity so that said microcapsules are self-supporting.

2. The method of claim 1 in which said sheet is disposed transverse to a vertical plane and said droplets pass downwardly through said sheet.

3. The method of claim 1 in which said biological substance comprises cells capable of secreting a selected biologically active product or of providing a selected biological function to an individual.

4. The method of claim 1 in which said sheet is maintained by surface tension contact with a solid boundary surface.

5. The method of claim 4 in which said solution is continuously fed to said boundary surface.

6. The method of claim 1 in which said polymer is a thermoplastic polymer.

7. The method of claim 6 in which said thermoplastic polymer is selected from the group consisting of polyacrylonitrile, polyvinyl chloride, polysulfone, cellulose acetate, and mixtures thereof.

8. The method of claim 1 in which the ratio of said polymer to said solvent in said sheet comprises from about 10% to 20%:

1 on a weight;

volume basis.

9. The method of claim 1 in which said polymer is an elastomeric polymer.

10. The method of claim 9 in which said elastomeric polymer comprises polyurethane.