Compositions and methods for nucleic acid delivery

Patent metadata

Field	Value
Publication number	US-9463244-B2
Application number	US-201414201615-A
Country	US
Kind code	B2
Filing date	Mar 7, 2014
Priority date	Mar 15, 2013
Publication date	Oct 11, 2016
Grant date	Oct 11, 2016

Abstract

The present invention provides, among other things, multilayer film coating compositions, coated substrates and methods thereof. In some embodiments, a structure includes a substrate; and a multilayer film coated on the substrate, wherein adjacent layers of the multilayer film are associated with one another via one or more non-covalent interactions, wherein the multilayer film comprises a first nucleic acid agent present at a loading density, and further wherein the multilayer film is characterized in that, when the structure is placed on a subject so that the multilayer film contacts cells, the first nucleic acid agent is released with a profile characterized by a feature selected from the group consisting of 1) being a burst-free release; 2) being a sustained release; and 3) exhibiting in vitro and/or in vivo biological effectiveness.

First claim

We claim:

1. A structure for localized and controlled release of nucleic acid agents comprising:
a bandage substrate; and
a multilayer film coated on the substrate, wherein adjacent layers of the multilayer film are associated with one another via one or more non-covalent interactions,
wherein the multilayer film includes:
a first bilayer portion; and
a second bilayer portion adjacent to the first bilayer portion, wherein the second bilayer portion is disposed on the bandage substrate, and

wherein:
the first bilayer portion includes at least fifty bilayers, each bilayer of the first bilayer portion comprising a first layer comprising an siRNA agent, and a second layer comprising chitosan,
the second bilayer portion includes at least ten bilayers, each bilayer of the second bilayer portion comprising a first layer comprising dextran sulfate and a second layer comprising a poly(β-amino ester) having the following structural formula:

wherein n is an integer greater than or equal to 5.

2. The structure of claim 1 , wherein loading density of the siRNA agent is at least about 1 μg/cm 2 , at least about 2 μg/cm 2 , at least about 5 μg/cm 2 , at least about 8 μg/cm 2 , at least about 10 μg/cm 2 , at least about 12 μg/cm 2 , at least about 15 μg/cm 2 , at least about 18 μg/cm 2 , at least about 20 μg/cm 2 , at least about 25 μg/cm 2 , at least about 30 μg/cm 2 , at least about 50 μg/cm 2 , or at least about 100 μg/cm 2 .

3. The structure of claim 1 , wherein the siRNA agent inhibits expression of a polypeptide.

4. The structure of claim 3 , wherein the polypeptide is selected from the group consisting of matrix metallopeptidase 9 (MMP-9), neutral endopeptidase (NEP) and protein tyrosine phosphatase 1B (PTP1B).

5. The structure of claim 1 , wherein the multilayer film comprises 60, 80, 100, 150 or 200 bilayers.

6. The structure of claim 1 , further comprising an additional agent.

7. The structure of claim 6 , wherein the additional agent is selected from one or more members of the group consisting of an antibiotic and an anti-inflammatory agent.

8. The structure of claim 1 , wherein the substrate comprises at least a portion of a medical device.

9. The structure of claim 1 , wherein the substrate is a wound dressing.

10. The structure of claim 1 , wherein the multilayer film further comprises a second nucleic acid agent present at a loading density of at least about 1 μg/cm 2 .

11. The structure of claim 10 , wherein the siRNA agent and second nucleic acid agent are presented at a predetermined ratio.

Assignees

• Masssachusetts Inst Of Tech
• Massachusetts Inst Technology

Inventors

• Castleberry Steven A
• Hammond Paula T

Classifications

• A61P17/02

  for treating wounds, ulcers, burns, scars, keloids, or the like · CPC title

• A61L31/16

  Biologically active materials, e.g. therapeutic substances {(A61L31/047 takes precedence)} · CPC title

• A61L2400/12

  Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces · CPC title

• A61L31/047

  Other specific proteins or polypeptides not covered by A61L31/044 - A61L31/046 · CPC title

• A61L2420/08

  Coatings comprising two or more layers · CPC title