Nanofibrous materials as drug, protein, or genetic release vehicles
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 from the fabric upon uptake of water from the ambient environment.
1. An electrospinning perfusion method for forming a fabricated textile comprising nanofibers suitable for use as a medical article, the method comprising steps of:
dissolving 19-20% weight per volume of a non-biodegradable polymer and a biologically-active agent in an organic solvent to provide an admixture, the dissolving step occurring at an ice-cold temperature of about 4° C., 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 perfusion process occurring at a temperature of about 25° C. to provide a perfused nanofibers, each having a diameter from 100 nm to 3000 nm; and
permitting trace solvent to be removed from the perfused nanofibers to form a biologically-active fabricated textile.
2. The method as recited in claim 1 , wherein the step of permitting trace solvent to be removed is performed using a post-treatment process performed after the step of perfusing the admixture.
3. The method as recited in claim 1 , wherein the target surface is a mandrel.
4. 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 solvent.
5. The method as recited in claim 1 , wherein the non-biodegradable polymer is selected from the group consisting of a non-biodegradable polyester, a polyurethane, and combinations thereof.
6. The method as recited in 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.
7. The method as recited in claim 1 , the method further comprising removing the fabricated textile from the target surface.
8. The method as recited in claim 3 , wherein the fabricated textile is formed into a tubular construct.
9. The method as recited in claim 8 , wherein the tubular construct has an internal diameter of at least 1 mm and less than 40 mm.
10. The method as recited in claim 8 , wherein the tubular construct has a length of at least about 1 cm and less than about 80 cm.
11. The method as recited in claim 7 , wherein the fabricated textile is formed into a rounded cuff shape.
12. The method as recited in claim 7 , wherein the fabricated textile is a flat sheet with a width of at least 1 cm and a length of at least 1 cm.
13. The method as recited in claim 12 , further comprising fusing the fabricating textile to a second flat sheet comprising a biodegradable polymer.
14. The method as recited in 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.
15. The method as recited in claim 1 , wherein the biologically-active agent is maintained at a temperature below about 50° C. during the steps of dissolving, loading, perfusing and permitting such that the biologically-active agent maintains the same biological activity after the method as the biologically-active agent had before the method.
16. The method as recited in claim 1 , wherein the target surface is a polytetrafluoroethylene coated ring that revolves about a central axle to create a torus configuration.
17. The method as recited in 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 as recited in claim 18 , wherein the fabricated textile has a single-strand yarn shape having 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.