Stable layer-by-layer coated particles

Patent metadata

Field	Value
Publication number	US-10278927-B2
Application number	US-201313869015-A
Country	US
Kind code	B2
Filing date	Apr 23, 2013
Priority date	Apr 23, 2012
Publication date	May 7, 2019
Grant date	May 7, 2019

Abstract

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

First claim

The invention claimed is:

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.

Assignees

• Massachusetts Inst Technology

Inventors

• Hammond Paula T
• Poon Zhiyong

Classifications

• A61K9/5146 Primary

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides · CPC title

• A61K9/5169

  Proteins, e.g. albumin, gelatin · CPC title

• A61K9/0019

  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 title

• A61K38/164

  from bacteria · CPC title

• A61K9/5161 Primary

  Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin · CPC title