Stable layer-by-layer coated particles

• US 10,278,927 B2
• Filed: 04/23/2013
• Issued: 05/07/2019
• Est. Priority Date: 04/23/2012
• Status: Active Grant

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Hammond, Paula T., Poon, Zhiyong
• Primary Examiner(s): Ahmed, Hasan S
• Application Number:
  US13/869,015
• Publication Number:
  US 20140093575A1
• Time in Patent Office: 2,205 Days
• CPC Class Codes: A61K 31/4188 condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
• CPC Class Codes: A61K 38/164 from bacteria
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/5146 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
• CPC Class Codes: A61K 9/5161 Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin
• CPC Class Codes: A61K 9/5169 Proteins, e.g. albumin, gelatin

Abstract

Systems and methods for coating a particle core with a layer-by-layer film are disclosed.

Claims

1. A particle, comprising:

a liposome core having a negatively charged outer surface and a diameter from about 100 nm to about 200 nm; and

a film coating the liposome core, the film comprising a first layer, a second layer, a third layer and a fourth layer, wherein;

the first layer, which coats the liposome core, includes poly-L-arginine (PLA);

the second layer, which coats the first layer, includes an siRNA therapeutic agent;

the third layer, which coats the second layer, includes PLA; and

the fourth layer, which coats the third layer, includes hyaluronic acid (HA),

and further wherein the liposome core comprises a second therapeutic agent.

2. The particle of claim 1, wherein the second therapeutic agent is doxorubicin.

3. The particle of claim 1, wherein the siRNA therapeutic agent is an siRNA targeting Multidrug Resistant Protein 1 (siRNA MRP1).

4. The particle of claim 1, wherein the particles includes about 3500 copies of siRNA.

5. The particle of claim 1, wherein the siRNA therapeutic agent is an siRNA targeting Multidrug Resistant Protein 1 (siRNA MRP1), the second therapeutic agent is doxorubicin, and the mass ratio of the siRNA therapeutic agent to doxorubicin is from about 1:

1 to about 1.25;

1.

6. A method of administering a combination of an siRNA therapeutic agent and a second therapeutic agent to a patient in need thereof, the method comprising:

administering to said patient a therapeutically effective amount of a pharmaceutical composition comprising the particles of claim 1 in a therapeutically acceptable carrier,

wherein the siRNA therapeutic agent and the second therapeutic agent are delivered to a tumor in a time-staggered manner.

7. The method of claim 6, wherein the particles includes about 3500 copies of siRNA.

8. The method of claim 7, wherein the siRNA therapeutic agent is an siRNA targeting Multidrug Resistant Protein 1 (siRNA MRP1), the second therapeutic agent is doxorubicin, and the mass ratio of the siRNA therapeutic agent to doxorubicin is from about 1:

1 to about 1.25;

1.