Electrospun cationic nanofibers and methods of making and using the same

Patent metadata

Field	Value
Publication number	US-10808335-B2
Application number	US-201816120988-A
Country	US
Kind code	B2
Filing date	Sep 4, 2018
Priority date	Apr 16, 2014
Publication date	Oct 20, 2020
Grant date	Oct 20, 2020

Abstract

Methods of making polycationic nanofibers by grafting cationic polymers onto electrospun neutral nanofibers and polycationic nanofibers produced by the methods are provided herein. In addition, methods of using the polycationic nanofibers to reduce inflammation, to adsorb anionic compounds such as heparin or nucleic acids, to inhibit the growth of microbes or inhibit the formation of a biofilm are also provided. The polycationic nanofibers may be in a mesh and may be included in a medical device, wound dressing, bandage, or as part of a graft.

First claim

We claim:

1. A method of using a polycationic nanofiber comprising administering the polycationic nanofibers to a subject in an amount effective to adsorb anionic compounds in the subject,
wherein the anionic compounds are pro-inflammatory or immunostimulatory anionic molecules or anionic anticoagulant polymers and
wherein the polycationic nanofiber is prepared by a method comprising (a) electrospinning a neutral polymer to produce nanofibers less than 2 μm in diameter and (b) grafting a cationic polymer onto the neutral polymer nanofibers to produce the polycationic nanofiber.

2. The method of claim 1 , wherein the administration and absorption is effective to reduce inflammation.

3. The method of claim 1 , wherein the polycationic nanofibers are administered in an amount effective to inhibit nucleic acid-induced activation of PRRs.

4. The method of claim 1 , wherein the polycationic nanofibers are administered in an amount effective to inhibit formation of a biofilm or inhibit growth of a microbe capable of forming a biofilm or infectious wound.

5. The method of claim 4 , wherein the biofilm comprises bacteria or fungi.

6. The method of claim 5 , wherein the bacteria are selected from the group consisting of Bacillus spp., Corynebacterium spp., Listeria spp. (i.e. Listeria monocytogenes ), Staphylococcus spp. (i.e. Staphylococcus aureus and Staphylococcus epidermis ), Micrococcus spp., and lactic acid bacteria (i.e. Lactobacillus plantarum, Lactococcus lactis, Entercoccus spp., Streptococcus spp. including Streptococcus mutans and Streptococcus pneumoniae ).

7. The method of claim 5 , wherein the bacteria are selected from the group consisting of Escherichia spp. (i.e. Escherichia coli ), Klebsiella spp. (i.e. Klebsiella pneumonia ), Pseudomonas spp. (i.e. Pseudomonas aeruginosa, Pseudomonas putida, Pseudomonas fluorescens ), Proteus spp., Legionella spp., Rhizobium spp. (i.e. Rhizobium leguminosarum ), Sinorhizobium spp. (i.e. Sinorhizobium meliloti ), and Serratia spp.

8. The method of claim 5 , wherein the fungi are selected from the group consisting of Candida and Aspergillus.

9. The method of claim 1 , wherein the polycationic nanofibers are incorporated into a medical device, filter, dressing, graft, or mesh.

10. The method of claim 1 , wherein the subject has an inflammatory disease or condition, an autoimmune disease, a chronic wound or has been treated with an anticoagulant.

11. The method of claim 1 , wherein the anionic compounds are pro-inflammatory or immunostimulatory anionic molecules.

12. The method of claim 1 , wherein the anionic compounds are anionic anticoagulant polymers.

13. The method of claim 1 , wherein the neutral polymer is poly-styrene maleic anhydride.

14. The method of claim 1 , wherein the cationic polymer is selected from the group consisting of polyethyleneimine (PEI), branched PEI (bPEI), polyamidoamine (PAMAM), in particular PAMAM generations 0-4 or other dendrimers, copolymers containing any combination of N,N′-cystaminebisacrylamide and N,N′-hexamethalyne bisacrylamide backbone components with histamine and 3-(dimethylamino)-1-propylamine linkers.

15. The method of claim 1 , wherein the nanofibers are between 0.1 μm and 2 μm in diameter.

Assignees

• Univ Duke

Inventors

• Sullenger Bruce A
• Juwarker Hemraj A
• Leong Kam W
• Gamboa Jackman Jennifer

Classifications

• B29C48/88 Primary

  Thermal treatment of the stream of extruded material, e.g. cooling · CPC title

• A61L15/46

  Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria · CPC title

• D06M15/285

  of unsaturated carboxylic acid amides or imides · CPC title

• A61L2300/41

  Anti-inflammatory agents, e.g. NSAIDs · CPC title

• D01F6/36

  comprising unsaturated carboxylic acids or unsaturated organic esters as the major constituent · CPC title