Nanofibrous materials as drug, protein, or genetic release vehicles
Inventors
Phaneuf, Matthew D. • Brown, Philip J. • Bide, Martin J.
Assignees
Rhode Island Board of Education • Clemson University • Biosurfaces Inc
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Publication Number
US-10441550-B2
Publication Date
2019-10-15
Expiration Date
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.
Core Innovation
The invention relates to forming a fabricated textile comprising nanofibers by electrospinning perfusion. A non-biodegradable polymer is dissolved in hexafluoroisopropanol at an ice-cold temperature to provide an admixture, and the admixture is loaded into an electrospinning perfusion instrument set at a specified flow rate.
An electric current of 15-20 kV is applied to a needle, and the admixture is perfused onto a target surface at a temperature between about 20 C and about 50 C while maintaining the specified flow rate. This provides a perfused nanofiber having a diameter from 100 nm to 3000 nm, and trace hexafluoroisopropanol is permitted to be removed from the perfused nanofiber to form the fabricated textile.
The disclosed approach is used to produce bioactive nanofibrous textiles that release biologically active agents when wetted by aqueous or organic fluids. Biologically active agents are incorporated into the non-biodegradable polymer admixture without harsh crosslinking/immersion steps, and biological activity is retained after immobilization.
Claims Coverage
The independent claim set includes one independent method claim with multiple dependent refinements. The inventive features focus on electrospinning perfusion of a non-biodegradable polymer dissolved in hexafluoroisopropanol at an ice-cold temperature, controlled electrical and temperature conditions during perfusion, generation of nanofiber diameters in a defined range, and removal of trace hexafluoroisopropanol to form a fabricated textile; additional dependents add biologically-active agents and specific end-use device formations.
Electrospinning perfusion to form nanofibrous fabricated textile
A method comprising electrospinning perfusion to form a fabricated textile comprising nanofibers by dissolving a non-biodegradable polymer in hexafluoroisopropanol to provide an admixture, loading the admixture into an electrospinning perfusion instrument set at a specified flow rate, applying an electric current of 15-20 kV to a needle, perfusing the admixture onto a target surface at the specified flow rate at 20 C to 50 C to provide a perfused nanofiber having a diameter from 100 nm to 3000 nm, and permitting trace hexafluoroisopropanol to be removed to form the fabricated textile.
Ice-cold hexafluoroisopropanol dissolution of non-biodegradable polymer
Dissolving a non-biodegradable polymer in hexafluoroisopropanol to provide an admixture, wherein the dissolving occurs at an ice-cold temperature.
Exclusion of specific polymers
The non-biodegradable polymer is not polytetrafluoroethylene, polypropylene, or polyethylene.
Defined perfusion temperature and nanofiber diameter range
Perfusing the admixture onto a target surface 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.
Trace hexafluoroisopropanol removal to form the textile
Permitting trace hexafluoroisopropanol to be removed from the perfused nanofiber to form a fabricated textile.
Biologically-active agent loaded polymer admixture
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.
Non-biodegradable polymer selection from polyester/polyurethane combinations
The non-biodegradable polymer is selected from a non-biodegradable polyester, a polyurethane, or combinations thereof.
Target surface embodiment and residual solvent removal
Using a metallic stent as the target surface, sliding the stent onto a mandrel, coating the mandrel with the perfused material, and air-drying in a vacuum oven at 37 C for 48 hours to remove residual hexafluoroisopropanol.
Defined jet gap between needle and target surface
A 15-30 centimeter jet gap exists between the needle and the target surface.
Scaffold-free medical device formation
The fabricated textile is formed into a medical device without the use of an underlying scaffold.
Across the independent method claim and its dependent refinements, the claim coverage centers on electrospinning perfusion using a non-biodegradable polymer dissolved in hexafluoroisopropanol, applying 15-20 kV, perfusing at 20 C to 50 C to produce nanofibers of 100-3000 nm diameter, and removing trace hexafluoroisopropanol to form the fabricated textile, with additional coverage for biologically-active agents, polymer class selection, specific target surface and jet gap constraints, residual solvent removal, and scaffold-free medical device formation.
Stated Advantages
Bioactive nanofibrous textiles release biologically active agents when wetted by aqueous or organic fluids.
Biologically active agents are incorporated without harsh crosslinking/immersion steps.
Biological activity is retained after immobilization.
The resulting materials are antimicrobial, antifungal, and otherwise biologically active.
Sustained release behavior is demonstrated by release profiling and bioactivity assays.
Documented Applications
Medical device formation without the use of an underlying scaffold.
Metallic stent embodiment as a target surface.
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