Compositions and methods for delivering an agent to a wound
The invention provides compositions featuring chitosan and methods for using such compositions for the local delivery of biologically active agents to an open fracture, complex wound or other site of infection. Advantageously, the degradation and drug elution profiles of the chitosan compositions can be tailored to the needs of particular patients at the point of care (e.g., in a surgical suite, clinic, physician's office, or other clinical setting).
1. A method for producing a biodegradable chitosan fiber or fiber composition having a desired biodegradation profile, the method comprising
(a) dissolving chitosan having a uniform degree of deacetylation of at least about 51% in one or more acids in an aqueous solvent, wherein the acid and solvent are selected such that the biodegradable chitosan fiber or fiber composition biodegrades over at least about one, two, three, four or five days in vivo;
(b) forming the chitosan of step (a) into a fiber or fiber composition by electrospinning;
(c) lyophilizing the fiber under conditions that reduce the water content by about 10% -100%;
(d) neutralizing the fiber or fiber composition by contacting the fiber or fiber composition with water, a neutral, or a basic solution, wherein the water, neutral, or basic solution is selected to modulate a physical-mechanical property of the fiber;
(e) washing the chitosan composition with water until neutral; and
(f) lyophilizing the fiber of step (e) to reduce the water content by about 80%-100%, thereby producing a biodegradable chitosan fiber.
2. The method of claim 1 , wherein the fiber is woven into a desired device.
3. The method of claim 1 , wherein the chitosan fiber or fiber composition is treated with an acid selected from the group consisting of acetic, citric, oxalic, proprionic, ascorbic, hydrochloric, formic, salicylic and lactic acids.
4. The method of claim 3 , wherein the acid solvent comprises lactic acid and/or acetic acid.
5. The method of claim 1 , wherein the fiber is spun to form a thread or suture, or is woven to form a fiber composition that is a mesh, strip, suture, dressing, or woven sheet.
6. A chitosan fiber or fiber composition produced by the method of claim 1 .
7. A wound management device comprising a chitosan fiber produced by the method of claim 1 .
8. The chitosan composition of claim 7 , wherein the chitosan degree of deacetylation, weight percent, neutralization solution, solvent make-up, and/or crystallinity is varied to customize the biodegradation profile, elution profile, and/or a physical-mechanical property of the chitosan composition.
9. The chitosan composition of claim 8 , wherein the physical-mechanical property is selected from the group consisting of tensile strength, Young's modulus, swelling, degradation, and a combination thereof.
10. The composition of claim 7 , wherein the acid is varied to customize the composition's degradation and elution rates.
11. A method for treating an infection in a subject at a site of trauma, the method comprising contacting the site with a wound management device comprising the chitosan composition produced according to claim 1 and an effective amount of at least one agent selected from the group consisting of antibacterial, antiviral and antifungal agents at a point of care.
12. A method for the local delivery of an agent to a site of trauma, the method comprising contacting the site with a chitosan composition of claim 1 comprising an agent selected at the point of care, thereby delivering the agent to the site, wherein the agent is selected from the group consisting of an antibacterial, antiviral and antifungal agent.
13. A medical device for implantation comprising a chitosan fiber or fiber composition of claim 1 and further comprising an effective amount of an agent selected from the group consisting of an antibacterial, antiviral or antifungal agent.
14. The wound management device of claim 7 comprising an effective amount of at least one agent selected from the group consisting of an antibacterial, antiviral or antifungal agent.