Nanofibrous materials as drug, protein, or genetic release vehicles

Patent metadata

Field	Value
Publication number	US-10441550-B2
Application number	US-201615046675-A
Country	US
Kind code	B2
Filing date	Feb 18, 2016
Priority date	Mar 4, 2005
Publication date	Oct 15, 2019
Grant date	Oct 15, 2019

Abstract

The present invention is a bioactive, nanofibrous material construct which is manufactured using a unique electrospinning perfusion methodology. One embodiment provides a nanofibrous biocomposite material formed as a discrete textile fabric from a prepared liquid admixture of (i) a non-biodegradable durable synthetic polymer; (ii) a biologically active agent; and (iii) a liquid organic carrier. These biologically-active agents are chemical compounds which retain their recognized biological activity both before and after becoming non-permanently bound to the formed textile material; and will become subsequently released in-situ as discrete freely mobile agents front the fabric upon uptake of water from the ambient environment.

First claim

What is claimed is:

1. A method of forming a fabricated textile comprising nanofibers by electrospinning perfusion, the method comprising the steps of:
dissolving 19-20% weight per volume of a non-biodegradable polymer in hexafluoroisopropanol to provide an admixture, the dissolving occurring at an ice-cold temperature, wherein the non-biodegradable polymer is not polytetrafluoroethylene, polypropylene, or polyethylene;
loading the admixture into an electrospinning perfusion instrument which can be set at a specified flow rate;
applying an electric current of 15-20 kV to a needle of the electrospinning perfusion instrument;
perfusing the admixture onto a target surface at the specified flow rate, the step of perfusing occurring at a temperature between about 20° C. and about 50° C. to provide a perfused nanofiber having a diameter from 100 nm to 3000 nm; and
permitting trace hexafluoroisopropanol to be removed from the perfused nanofiber to form a fabricated textile.

2. The method of claim 1 , further comprising dissolving at least one biologically-active agent such that the admixture comprises a mixture of the non-biodegradable polymer and the at least one biologically active agent.

3. The method of claim 1 , wherein the step of permitting trace hexafluoroisopropanol to be removed is performed using a post-treatment process performed after the step of perfusing the admixture.

4. The method of claim 1 , wherein the target surface is a mandrel.

5. The method of claim 1 , wherein the target surface is a metallic stent that is slid onto a mandrel and coated with perfused material, and wherein the coated metallic stent is air-dried in a vacuum oven at 37° C. for 48 hours to remove residual hexafluoroisopropanol.

6. The method of claim 1 , wherein the non-biodegradable polymer is selected from the group consisting of a non-biodegradable polyester, a polyurethane, and combinations thereof.

7. The method of claim 1 , wherein the target surface comprises a first portion and a second portion and the step of perfusing the admixture onto the target surface perfuses the admixture for a first period of time onto the first portion and for a second period of time onto the second portion, wherein the first period and the second period are different.

8. The method of claim 1 , the method further comprising removing the perfused fabricated textile from the target surface.

9. The method of claim 4 , wherein the perfused fabricated textile is formed into a tubular construct.

10. The method of claim 9 , wherein the tubular construct has an internal diameter of at least 1 mm and less than 40 mm.

11. The method of claim 9 , wherein the tubular construct has a length of at least about 1 cm and less than about 80 cm.

12. The method of claim 4 , wherein the perfused fabricated textile coated mandrel is processed to remove traces of residual solvent and one edge of the perfused material is rolled towards an opposite end of the mandrel to achieve a desired thickness, and wherein the perfused material is cut along an opposite edge and the opposite edge is fused to form a rounded cuff shape.

13. The method of claim 8 , wherein the perfused fabricated textile is a flat sheet with a width of at least 1 cm and a length of at least 1 cm.

14. The method of claim 13 , further comprising fusing the perfused fabricated textile to a second flat sheet comprising a biodegradable polymer.

15. The method of claim 1 , wherein the step of dissolving further comprises dissolving a biodegradable polymer such that the admixture comprises a mixture of the non-biodegradable polymer and the biodegradable polymer.

16. The method of claim 2 , wherein the at least one biologically-active agent is maintained at a temperature below about 50° C. during the steps of dissolving, loading, perfusing and permitting such that the at least one biologically active agent maintains the same biological activity after the method as the at least one biologically active agent had before the method.

17. The method of claim 1 , wherein the target surface is configured to create alignment of polymer nanofibers in a toroidal direction with respect to a revolution of the target surface.

18. The method of claim 17 , wherein the polymer nanofibers are removed from the target surface and manually twisted and elongated to their yield strain to produce a single-strand yarn shape.

19. The method of claim 18 , wherein the single-strand yarn shape has a diameter between about 0.025 mm and about 2 mm.

20. The method of claim 1 , wherein a 15-30 centimeter jet gap exists between the needle and the target surface.

21. The method of claim 1 , wherein a 15 centimeter jet gap exists between the needle and the target surface.

22. The method of claim 1 , wherein the fabricated textile is formed into a medical device without the use of an underlying scaffold.

Assignees

• Biosurfaces Inc
• Univ Clemson
• Rhode Island Board Of Education

Inventors

• Phaneuf Matthew D
• Brown Philip J
• Bide Martin J

Classifications

• D01D1/02

  Preparation of spinning solutions · CPC title

• D04H1/728

  by electro-spinning {(electro-spinning methods and apparatus D01D5/0007)} · CPC title

• B29C48/05

  Filamentary, e.g. strands · CPC title

• D01F6/62

  from polyesters · CPC title

• B29C48/022

  characterised by the choice of material · CPC title