Production of nanocapsules and microcapsules by layer-wise polyelectrolyte self-assembly

• US 7,101,575 B2
• Filed: 02/27/2003
• Issued: 09/05/2006
• Est. Priority Date: 03/19/1998
• Status: Expired due to Fees

• Current Assignee: Max-Planck-Gesellschaft Zur Foerderung Der Wissenschaften e.V. (Max-Planck-Gesellschaft zur Frderung der Wissenschaften e)
• Original Assignee: Max-Planck-Gesellschaft Zur Foerderung Der Wissenschaften e.V. (Max-Planck-Gesellschaft zur Frderung der Wissenschaften e)
• Inventors: Sukhorukov, Gleb B., Bäumler, Hans, Lerche, Karl-Heinz, Voigt, Andreas, Caruso, Frank, Möhwald, Helmuth, Donath, Edwin
• Primary Examiner(s): Woodward, Michael P.
• Assistant Examiner(s): Fitzgerald, Marc C.
• Application Number:
  US10/376,386
• Publication Number:
  US 20030219384A1
• Time in Patent Office: 1,286 Days
• Field of Search: 424/463, 424/489
• US Class Current: 424/489
• CPC Class Codes: A61K 9/5015 Organic compounds, e.g. fats, sugars
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• 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 9/5052 Proteins, e.g. albumin
• CPC Class Codes: A61K 9/5073 having two or more different coatings optionally including drug-containing subcoatings
• CPC Class Codes: A61K 9/5089 Processes
• CPC Class Codes: A61K 9/51 Nanocapsules; Nanoparticles; nanotubes A61K9/0092; polymeric micelles A61K9/1075; polymersomes A61K9/1273; pure drug nanoparticles A61K9/14; drug nanoparticles with adsorbed surface modifiers A61K9/141; conjugates, e.g. between drug and non-active nanoparticles, A61K47/50; preparations for in vivo diagnosis A61K49/00; with radioactive substances A61K51/00
• CPC Class Codes: A61K 9/5138 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/5192 Processes
• CPC Class Codes: B01J 13/02 Making microcapsules or microballoons for medical preparations A61K9/50
• CPC Class Codes: B01J 13/22 Coating

Abstract

The invention relates to capsules coated with a polyelectrolyte shell and methods for the production thereof.

Claims

1. A capsule with a polyelectrolyte shell, comprising an active ingredient and a plurality of polyelectrolyte layers, and a diameter of up to 10 μ

m, wherein the shell comprises alternate layers of cationic and anionic polyelectrolytes.

2. A capsule claimed in claim 1 having a diameter of less than or equal to 5 μ

m.

3. A capsule as claimed in claim 1, prepared by applying polyelectrolyte molecules to a template particle.

4. A capsule as claimed in claim 3, wherein the template particle is in interior of the capsule.

5. A capsule as claimed in claim 3, wherein the template particle is at least partly disaggregated.

6. A capsule as claimed in claim 1, further comprising a liquid phase, wherein said liquid phase is inside the shell.

7. A capsule as claimed in claim 1, wherein the active ingredient is selected from the group consisting of catalysts, nanoparticles, active pharmaceutical ingredients, sensor molecules, crystals, polymers and gases.

8. A capsule as claimed in claim 1, wherein the shells comprise pores.

9. A capsule as claimed in claim 1, wherein the pores permit substances with a molecular weight of ≦

4 kD to pass through.

10. A capsule as claimed in claim 1, wherein the shell further comprises at least one member selected from the group consisting of nanoparticles, surfactants and lipids.

11. A capsule as claimed in claim 1, wherein the thickness of the shell wall is from 2 to 100 nm.

12. A composition which comprises a plurality of capsules as claimed in claim 1, with a monodisperse size distribution.

13. A composition which comprises capsules as claimed in claim 1, in dried, frozen or freeze-dried form.

26. A capsule as claimed in claim 7, wherein said catalyst is an enzyme.

14. A method for the production of capsules coated with a polyelectrolyte shell comprising an active ingredient and a plurality of alternating layers of cationic and anionic polyelectrolytes wherein the diameter is ≦

10 μ

m and the method comprises the steps of;

a) preparing an acqueous dispersion of template particles of suitable size and

b) producing a sheel around the particles by application of polyelectrolytes to the template particles.

15. A method as claimed in claim 14, wherein said template particles are soluble particles.

16. A method as claimed in claim 14, wherein said template particles are aggregates of subparticles.

17. A method as claimed in claim 16, wherein preformed aggregates are produced by applying at least one of an electrical field or a magnetic field to a suspension of subparticles.

18. A method as claimed in claim 14, wherein successive layers of in each case oppositely charged polyelectrolytes are applied to the template particles.

19. A method as claimed in claim 14, further comprising the step of:

(c) disintegration of the template particles.

20. A method as claimed in claim 19, wherein the template particles are disintegrated by at least one of changing the pH or sulfonating the template particles.

21. A method as claimed in claim 19, further comprising the step of:

(d) removal of template particle fragments.

22. A method as claimed in claim 14, wherein the capsules are loaded with an active ingredient before, during or after the coating.

23. A method as claimed in claim 22, wherein the capsule is loaded with low molecular weight substances through pores in the shell wall.

24. A method as claimed in claim 22, wherein the active ingredient is immobilized onto the template particles or taken up by the template particles before application of the coating.

25. A method for the production of a coated surface, which comprises adding capsules as claimed in claim 14 to a surface.

27. A method as claimed in claim 15, wherein said soluble particles are partially crosslinked melamine-formaldehyde particles.