Thin film cell encapsulation devices

Patent metadata

Field	Value
Publication number	US-10865378-B2
Application number	US-201816111773-A
Country	US
Kind code	B2
Filing date	Aug 24, 2018
Priority date	Mar 23, 2015
Publication date	Dec 15, 2020
Grant date	Dec 15, 2020

Abstract

Thin film devices, e.g., multilayer thin film devices, that encapsulate cells for transplantation into a subject are provided. Also provided are methods of using and methods of preparing the subject devices. The thin film devices include a first porous polymer layer and a second porous polymer layer that define a lumen therebetween and encapsulate a population of cells within the lumen. The thin film devices can promote vascularization into the lumen of the device via the pores in the first polymer layer and/or second polymer layer; limit foreign body response to the device; limit ingress of cells, immunoglobulins, and cytokines into the lumen via the first and the second polymer layers; and release from the first polymer layer and/or the second polymer layer molecules secreted by the population of cells.

First claim

What is claimed is:

1. A method of treating a subject in need of a therapeutic molecule, said method comprising:
(a) introducing into said subject a device comprising:
(i) a lumen containing a plurality of cells capable of secreting the therapeutic molecule; and
(ii) a layer comprising a biocompatible polymer surrounding said lumen and comprising a plurality of pores sized such that said therapeutic molecule can diffuse from said device, wherein said plurality of pores are nanopores; and
(b) secreting, from said plurality of cells, said therapeutic molecule at a therapeutically effective amount for at least 30 days, wherein said plurality of cells are selected from the group consisting of: allogeneic cells and xenogeneic cells, and wherein said subject has not received immunosuppression therapy.

2. The method of claim 1 , wherein said layer of biocompatible polymer comprises a first layer of biocompatible polymer and a second layer of biocompatible polymer, wherein said lumen is disposed between said first layer of biocompatible polymer and said second layer of biocompatible polymer.

3. The method of claim 1 , wherein said biocompatible polymer is selected from the group consisting of: methacrylate polymer, polyethyleneimine, polyethyleneimine-dextran sulfate, poly(vinylsiloxane) ecopolymerepolyethyleneimine, phosphorylcholine, poly(ethyl methacrylate), polyurethane, poly(ethylene glycol), poly(lactic-glycolic acid), hydroxyapatite, poly(lactic acid), polyhydroxyvalerte and copolymers thereof, polyhydroxybutyrate and copolymers thereof, polycaprolactone, polydiaxanone, polyanhydride, polycyanocrylate, poly(amino acids), poly(orthoesters), polyesters, collagen, gelatin, cellulose polymer, chitosans, alginates, and any combination thereof.

4. The method of claim 3 , wherein said biocompatible polymer comprises polycaprolactone.

5. The method of claim 1 , wherein said therapeutic molecule has a molecular weight of less than 10 kDa.

6. The method of claim 1 , wherein said therapeutic molecule has a hydrodynamic radius of less than 2 nm.

7. The method of claim 1 , wherein said plurality of pores are sized such that a concentration of cytokines that is capable of accessing said lumen is below a level required for an immune response against said plurality of cells.

8. The method of claim 7 , wherein said cytokines have a molecular weight of greater than 15 kDa.

9. The method of claim 7 , wherein said cytokines have a hydrodynamic radius of greater than 2 nm.

10. The method of claim 7 , wherein said cytokines are selected from the group consisting of: interferons, interleukins, and tumor necrosis factors.

11. The method of claim 1 , wherein said nanopores have an average diameter from 5 nm to 500 nm.

12. The method of claim 1 , wherein said nanopores have an average diameter from 10 nm to about 300 nm.

13. The method of claim 1 , wherein said first layer of biocompatible polymer and said second layer of biocompatible polymer each have a thickness of less than 15 μm.

14. The method of claim 1 , wherein said device has a thickness of less than 30 μm.

15. The method of claim 1 , wherein said introducing comprises transplanting said device subcutaneously into said subject.

16. The method of claim 1 , wherein said subject has or is predisposed to developing Type I diabetes.

17. The method of claim 16 , wherein said plurality of cells comprise insulin-secreting cells.

18. The method of claim 17 , wherein said therapeutic molecule is insulin.

19. The method of claim 17 , wherein said insulin-secreting cells have a glucose stimulation index (GSI) that is not statistically significantly changed over a period of at least 30 days after introducing said device into said subject.

20. The method of claim 1 , wherein said device is substantially planar.

Assignees

• Univ California

Inventors

• Desai Tejal A
• Nyitray Crystal
• Chang Ryan

Classifications

• A61K9/0024 Primary

  Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue (compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L) · CPC title

• C12N5/0012 Primary

  Cell encapsulation · CPC title

• C08G63/08

  Lactones or lactides · CPC title

• A61F2/022

  Artificial gland structures using bioreactors (hemodialysis A61M1/16; hemofiltration A61M1/34; other extracorporeal blood treatment A61M1/36) · CPC title

• A61K47/34

  Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence) · CPC title