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

• US 8,168,226 B2
• Filed: 08/10/2006
• Issued: 05/01/2012
• 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: Donath, Edwin, Sukhorukov, Gleb B., Lerche, Karl-Heinz, Voigt, Andreas, Bäumler, Hans, Caruso, Frank, Möhwald, Helmuth
• Primary Examiner(s): TRAN, SUSAN T
• Application Number:
  US11/502,180
• Publication Number:
  US 20060275373A1
• Time in Patent Office: 2,091 Days
• Field of Search: None
• US Class Current: 424/490
• 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 method comprising applying a plurality of layers of coating substances to soluble template particles by:

(a) contacting the soluble template particles with a first coating substance in a fluid reaction medium in a reaction chamber which is limited on at least one side by a filtration membrane, under conditions with which a layer of the first coating substance is formed on the soluble template particles;

(b) draining at least part of the reaction medium with, where appropriate, excess first coating substance present therein through the filtration membrane into a filtrate chamber;

(c) contacting the soluble template particles with a second coating substance in a fluid reaction medium in a reaction chamber which is limited on at least one side by a filtration membrane, under conditions with which a layer of the second coating substance is formed on the soluble template particles;

(d) draining at least part of the reaction medium with, where appropriate, excess second coating substance present therein through the filtration membrane into a filtrate chamber; and

(e) optionally repeating steps (a) and (b) or steps (c) and (d) a plurality of times,

wherein the first and second coating substances are oppositely charged species or mixtures of polyelectrolyte species, wherein the soluble template particles have a diameter of up to 10 μ

m, and wherein the method further comprises a disaggregation of the soluble template particles after the completion of step (e).

2. A method according to claim 1, wherein the soluble template particles are selected from biological particles or aggregates.

3. A method according to claim 1, wherein a washing medium is added during or after step (b) or step (d).

4. A method according to claim 3, wherein the addition of the washing medium takes place so that the volume of the medium remains essentially constant in step (b) or step (d).

5. A method according to claim 1, wherein the filtration is carried out essentially without a pressure difference between reaction chamber and filtrate chamber.

6. A method according to claim 1, wherein the reaction chamber is stirred at least during step (a) or (c).

7. A method according to claim 1, wherein the reaction chamber is stirred throughout the process.