Polycationic microfibers and methods of using the same

Patent metadata

Field	Value
Publication number	US-12447464-B2
Application number	US-201716472735-A
Country	US
Kind code	B2
Filing date	Dec 22, 2017
Priority date	Dec 22, 2016
Publication date	Oct 21, 2025
Grant date	Oct 21, 2025

Abstract

Disclosed herein are polycationic microfibers comprising a high-aspect-ratio polymeric core, the polymeric core comprising a blend of a first core polymer and a second core polymer, and a polycationic polymer immobilized on the surface of the polymeric core. The polycationic microfibers are capable of sequestering or clearing nucleic acids, proteins, biomolecular complexes, exosomes, or microparticles from solutions and samples and may be formed into filters or integrated into filtration apparatuses. Also disclosed are methods for sequestering or clearing solutes from solutions and fluids, methods for the treatment of diseases or conditions, and methods for the prevention of diseases or conditions.

First claim

We claim:

1. A polycationic microfiber comprising
a high-aspect-ratio polymeric core, the polymeric core consisting of a blend of a first core polymer and a second core polymer; and
a polycationic polymer immobilized on the surface of the polymeric core;
wherein the weight ratio of the first core polymer to the second core polymer is about 1.5:1 to about 1:1.5; and
wherein the first core polymer consists of poly(styrene-alt-maleic anhydride).

2. The polycationic microfiber of claim 1 ,
wherein the first core polymer is a copolymer comprising residues of a first monomer and a second monomer;
wherein the second core polymer comprises residues of the first monomer; and
wherein the polycationic polymer is immobilized preferentially to the residues of the second monomer of the first core polymer.

3. The polycationic microfiber of claim 1 , wherein the second core polymer comprises polystyrene.

4. The polycationic microfiber of claim 1 , wherein the polymeric core has a mean diameter greater than 2 microns.

5. The polycationic microfiber of claim 1 , wherein the polymeric core comprises a first binding moiety, the polycationic polymer comprises a second binding moiety, and the first binding moiety and the second binding moiety have an affinity for each other.

6. The polycationic microfiber of claim 5 , wherein the first binding moiety or the second binding moiety is biotin, a biotin-binding moiety, avidin, an avidin-binding moiety, an antigen, an antigen-binding moiety, an antibody, or an antibody-binding moiety.

7. The polycationic microfiber of claim 1 , wherein the polycationic polymer comprises poly(β amino ester), disulfide containing poly(β amido amine) or poly(β hydroxyl amine).

8. A filter, the filter comprising the polycationic microfiber of claim 1 , wherein the polycationic microfiber forms a porous mesh.

9. An extracorporeal filtration apparatus for sequestering a nucleic acid, a protein, a polysaccharide, a glycosaminoglycan, a biomolecular complex, an exosome, or a microparticle from a subject in need of a treatment for a disease or a condition or for the prevention of the onset of a disease or condition, the filtration apparatus comprising:
(a) a first end of a blood line configured to interface with a first blood vessel of the subject for the removal of blood from the subject;
(b) a second end of the blood line configured to interface with a second blood vessel of the subject for the return of blood to the subject;
(c) a blood pump positioned along the blood line between the first end and the second end configured for the extracorporeal circulation of blood from the first end to the second end; and
(d) a filter comprising the polycationic microfiber of claim 1 formed into a porous mesh positioned along the blood line between the first end and the second end, wherein the polycationic microfiber is configured to bind or sequester the nucleic acid, the protein, the polysaccharide, the glycosaminoglycan, the biomolecular complex, the exosome, or the microparticle from the subject.

10. An ex vivo perfusion or filtration machine, the machine comprising:
(a) a housing configured to host a tissue, a graft, or a organ;
(b) a first end of a line configured to interface with the tissue, the graft, or the organ and allow for the introduction of a perfusate to the tissue, the graft, or the organ;
(c) a second end of the line configured to interface with the tissue, the graft, or the organ and allow for the removal of the perfusate from the tissue, the graft, or the organ;
(d) a pump positioned along the line between the first end and the second end configured for the circulation of the perfusate from the second end to the first end; and
(e) a filter comprising the polycationic microfiber of claim 1 formed into a porous mesh positioned along the line between the first end and the second end, wherein the polycationic microfiber is configured to bind or sequester a nucleic acid, a protein, a polysaccharide, a glycosaminoglycan, a biomolecular complex, a exosome, or a microparticle in the perfusate.

11. A method of sequestering a nucleic acid, a protein, a biomolecular complex, an exosome, or a microparticle from a solution or a sample, the method comprising contacting the solution or the sample comprising the nucleic acid, the protein, the biomolecular complex, the exosome, or the microparticle with the polycationic microfiber of claim 1 .

12. A method of treating a subject suffering from a disease or condition, the method comprising administering a therapeutically effective amount of a solute-cleared fluid to the subject, wherein the solute-cleared fluid is prepared from a bodily fluid and wherein the solute-cleared fluid is prepared by contacting the bodily fluid with the polycationic microfiber of claim 1 .

13. The method of claim 12 , wherein the solute-cleared fluid is administered continuously.

14. A method for the prevention of a disease or a condition in a subject, the method comprising administering an effective amount of a solute-cleared fluid to the subject following organ transplantation, wherein the solute-cleared fluid is prepared from a bodily fluid and wherein the solute-cleared fluid is prepared by contacting the bodily fluid with the polycationic microfiber of claim 1 .

15. The method of claim 14 , wherein the solute-cleared fluid is administered continuously.

16. A method for the prevention of injury to or dysfunction of tissue, a graft, or an organ to be transplanted into a subject, the method comprising administering an effective amount of a solute-cleared fluid to the tissue, the graft, or the organ, wherein the solute-cleared fluid is prepared from a perfusate, wherein the solute-cleared fluid is prepared by contacting the bodily fluid with the polycationic microfiber of claim 1 .

17. A method for the reduction of inflammation, thrombosis, or rejection or a tissue, a graft, or an organ after transplantation of the tissue, the graft, or the organ into a subject, the method comprising administering an effective amount of a solute-cleared fluid to the tissue, the graft, or the organ, wherein the solute-cleared fluid is prepared from a perfusate, wherein the solute-cleared fluid is prepared by contacting the bodily fluid with the polycationic microfiber of claim 1 .

Assignees

• Univ Duke

Inventors

• Lee Jaewoo
• Sullenger Bruce A
• Jackman Jennifer G

Classifications

• A01N1/143

  for organ perfusion · CPC title

• B01D71/281

  Polystyrene · CPC title

• B01D69/1411

  containing dispersed material in a continuous matrix · CPC title

• B01D71/401

  Polymers based on the polymerisation of acrylic acid, e.g. polyacrylate · CPC title

• B01D67/00042

  by deposition of fibres, nanofibres or nanofibrils · CPC title