Encapsulating particles with coatings that conform to size and shape of the particles

• US 6,558,665 B1
• Filed: 05/18/2000
• Issued: 05/06/2003
• Est. Priority Date: 05/18/1999
• Status: Expired due to Fees

• Current Assignee: ARCH Development Corporation (University of Chicago)
• Original Assignee: ARCH Development Corporation (University of Chicago)
• Inventors: Cohen, Itai, Nagel, Sidney, Rilo, Horacio, Mrksich, Milan
• Primary Examiner(s): Naff, David M.
• Application Number:
  US09/575,844
• Time in Patent Office: 1,083 Days
• Field of Search: 435/174, 435/177, 435/178, 435/180, 435/382, 424/93.7
• US Class Current: 424/93.7
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• 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 9/5089 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 11/089 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: C12N 11/098 formed in the presence of the enzymes or microbial cells
• CPC Class Codes: C12N 11/10 the carrier being a carbohydrate
• CPC Class Codes: C12N 5/0676 Pancreatic cells

Abstract

Particles such as islet cells are encapsulated by a method that forms a coating of uniform thickness that conforms to the size and shape of the particles. Two substantially immiscible liquids of different densities are provided in a container as upper and lower liquids such that an interface exists between the liquids. The upper liquid is less dense and has a greater viscosity than the lower liquid which is a coating liquid containing particles to be encapsulated. A tube is positioned in the upper liquid such that an orifice of the tube is above the interface. A pump connected to the tube sucks liquid through the tube at a rate sufficient to form a spout containing substantially the lower liquid extending between the interface and the tube orifice. The spout has maximum diameter at the interface and decreases in diameter as the spout approaches the tube orifice. Particles in the lower liquid are drawn up through the spout as liquid is withdrawn, and coated particles are released from the spout at a point where the diameter of the spout is less than the diameter of the particles, and the coated particles flow through the tube. The coating liquid may be a pre-polymer that can be polymerized and crosslinked after coating. The coated particles have therapeutic applications such as administering coated islet cells to treat diabetes.

Claims

1. A method for encapsulating particles, the method comprising:

providing a container having two liquids therein, said liquids having different densities and being substantially immiscible relative to each other and being situated in said container such that an interface exists between the liquids, the liquid of lesser density comprising an upper liquid and the liquid of greater density comprising a lower liquid, the lower liquid comprising a coating liquid and having said particles to be coated entrained therein, the upper liquid having a greater viscosity than the lower liquid;

inserting a tube having an orifice into the container such that said orifice is positioned in the upper liquid above said interface, said tube being operably connected to a pump for withdrawing liquid from the container;

activating said pump and establishing a pumping rate sufficient to form a spout extending between said interface and said orifice of said tube, said spout substantially comprising said lower liquid being withdrawn from said container, said spout having a maximum diameter base portion at said interface and decreasing in diameter as the spout approaches said tube, said base portion diameter being greater than the diameters of the particles to be coated, said pumping rate being sufficient to draw said particles from said lower liquid and through the spout;

coating a particle by drawing the particle upwardly through said spout from said base portion wherein the particle is engulfed by a coating of said spout liquid, to an upper spout portion, said upper spout portion having a diameter less than the diameter of the particle, thereby causing a break in said spout and freeing said coated particle for flow through said tube;

re-establishing said spout by continuing said pumping at said sufficient pumping rate, and coating additional particles by drawing each particle to be coated upwardly through said spout from said base portion to an upper portion of said re-established spout having a diameter less than the diameter of the particle being coated, thereby causing a break in said spout and freeing said coated particle;

repeating said coating process until all of said particles to be coated have been drawn upwardly through said spout and coated with said spout liquid; and

collecting said coated particles.

2. The method of claim 1, wherein said coating liquid comprises a pre-polymer liquid.

3. The method of claim 2, further comprising, after the step of coating one of the particles, polymerizing said pre-polymer liquid, and cross-linking said polymerized coating into a hard coat.

4. The method of claim 3, wherein said polymerized coating is cross-linked by shining an ultraviolet light on the coating.

5. The method of claim 3, wherein said polymerized coating is cross-linked by passing the polymer through a temperature gradient.

6. The method of claim 3, wherein said polymerized coating is cross-linked by a chemical initiation reaction.

7. The method of claim 1, wherein said tube comprises a pipette having an inner diameter of about 0.5 cm.

8. The method of claim 1, wherein said upper fluid comprises an oil having a viscosity of about 200 centi-Stokes.

9. The method of claim 1, wherein the lower liquid comprises a solution of poly(ethylene glycol) having a viscosity between about 1 and 50 centi-Stokes.

10. The method of claim 1, wherein said particles to be coated have a diameter between about 100 and 800 microns.

11. The method of claim 1, wherein said particles to be coated have a diameter between about 100 and 300 microns.

12. The method of claim 11, wherein said particles to be coated have a diameter of approximately 200 microns, and wherein the coating conforms to the size and shape of the particle and has a thickness of approximately 10-15 microns.

13. The method of claim 1, wherein a plurality of tubes are inserted into the upper liquid, each of said tubes being operably connected to a pump for withdrawing liquid from the container and for coating particles drawn through each of said tubes.

14. The method of claim 1, wherein a plurality of tubes are inserted into the upper liquid, each of said tubes being operably connected to a separate pump for withdrawing liquid from the container and for coating particles drawn through said tube.

15. The method of claim 1, wherein the particle is a cell.

16. The method of claim 15, wherein the cell is an islet cell.

17. A coated islet cell encapsulated by the method of claim 1, wherein the islet cell has an outer coating of uniform thickness that conforms to the size and shape of the cell.

18. The coated islet cell of claim 17, wherein the outer coating has a thickness of about 10-15 microns.

19. A method of treating a patient with diabetes comprising administering a pharmaceutically effective amount of the coated islet cell of claim 17.

20. A method of providing a therapeutic compound to a patient comprising administering a pharmaceutically effective amount of a coated particle encapsulated by the method of claim 1.