System and method to use suction to enhance permeabilization and transfection of cells

Patent metadata

Field	Value
Publication number	US-12508409-B2
Application number	US-202117306881-A
Country	US
Kind code	B2
Filing date	May 3, 2021
Priority date	May 4, 2020
Publication date	Dec 30, 2025
Grant date	Dec 30, 2025

Abstract

A method and apparatus for promoting the delivery of a molecule across a cell membrane comprises delivering a molecule to a delivery site of a region of tissue surrounding the cell membrane. A suction component applies a suction through a suction tip that surrounds the surface of the delivery site creating a seal to promote delivery of the molecule across the cell membrane. The application of the suction is controlled to create a predetermined negative pressure for a predetermined period of time before releasing the negative pressure. Suction is used to enhance permeabilization and transfection of cells. The technique can be used to enhance the uptake and subsequent transfection and expression of plasmid DNA vaccines, mRNA vaccines and other nucleic acid molecules, that are introduced subcutaneously. It can be used in combination with coated microneedles.

First claim

What is claimed is:

1 . A device to promote delivery of a molecule across a cell membrane, the device comprising:
a suction component configured to create a predetermined negative pressure; a disposable suction tip connected to the suction component and configured to form a seal along surface tissue to surround a molecule delivery site for applying the predetermined negative pressure; an insertion component including a microneedle including a coating that comprises the molecule, the molecule comprising a dried nucleic acid vaccine, the insertion component being configured to deliver the molecule to the molecule delivery site prior to applying the predetermined negative pressure; and a controller configured to apply the predetermined negative pressure for a predetermined period of time and then release the negative pressure, the controller being further configured to delay applying the predetermined negative pressure until after the insertion component is withdrawn from the surface tissue and for sufficient time after delivering the molecule to the tissue to permit hydrating and dispersing of the dried nucleic acid vaccine into the surface tissue.

2 . The device of claim 1 , wherein the predetermined negative pressure is between 40 kPa and 90 kPa.

3 . The device of claim 1 , wherein the predetermined period of time to apply the predetermined negative pressure is between 1 and 40 seconds.

4 . The device of claim 1 , wherein the predetermined period of time to apply the predetermined negative pressure is approximately 30 seconds.

5 . The device of claim 1 , wherein the disposable suction tip is further configured such that the seal forms a circle along the surface tissue.

6 . The device of claim 5 , wherein the circle has approximately a 6 mm diameter and a seal thickness of approximately 1 to 1.5 mm.

7 . The device of claim 6 , wherein the disposable suction tip is configured to form a secondary seal surrounding the molecule delivery site.

8 . The device of claim 1 , wherein the disposable suction tip is further configured such that the seal forms an equilateral concave decagon along the surface tissue.

9 . The device of claim 1 , wherein the disposable suction tip may be interchangeably substituted with disposable suction tips having various shapes and sized seals selected based on a delivery protocol of the surface tissue or the molecule delivered.

10 . The device of claim 1 , wherein the disposable suction tip includes an internal filter.

11 . The device of claim 10 , wherein the filter is configured to prevent liquids from entering the suction component.

12 . The device of claim 1 , wherein the nucleic acid vaccine comprises a plasmid DNA vaccine.

13 . The device of claim 1 , wherein the nucleic acid vaccine comprises an mRNA vaccine.

14 . The device of claim 1 , wherein the microneedle comprises a length configured to deliver the molecule to an epidermal or dermal layer of skin.

15 . The device of claim 1 , wherein the coating comprises a matrix material.

16 . The device of claim 15 , wherein the matrix material comprises at least one of: a polysaccharide, a protein, an enzyme, and a water soluble polymer.

17 . The device of claim 1 , wherein the microneedle comprises a length of about 2 mm or less.

18 . The device of claim 1 , wherein, after releasing the negative pressure, the controller is configured to re-apply negative pressure for a second period of time and then release the re-applied negative pressure.

19 . The device of claim 1 , wherein the molecule is delivered as part of a molecular complex.

20 . The device of claim 1 , wherein the time after delivering the molecule to the tissue is less than one minute.

Assignees

• Univ Rutgers

Inventors

• Lin Hao
• Singer Jonathan P
• Shreiber David I
• Shan Jerry W
• Zahn Jeffrey D
• Lallow Emran O
• Melnik Juliet M
• Jhumur Nandita Chakrabarty

Classifications

• A61M2037/0023

  Drug applicators using microneedles · CPC title

• A61M2037/0007

  having means for enhancing the permeation of substances through the epidermis, e.g. using suction or depression, electric or magnetic fields, sound waves or chemical agents · CPC title

• A61K2039/53

  DNA (RNA) vaccination · CPC title

• A61K39/00

  Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53) · CPC title

• A61K9/0021

  Intradermal administration, e.g. through microneedle arrays or needleless injectors · CPC title