Methods for producing a biodegradable chitosan composition and uses thereof
The invention provides improved methods for generating biodegradable chitosan compositions, and therapeutic methods of using such compositions to deliver therapeutic agents.
1. A method for producing a biodegradable chitosan film or sponge, the method comprising
(a) dissolving chitosan in a 3:1 ratio of lactic and acetic acid solution;
(b) forming the chitosan into a desired shape and lyophilizing the chitosan to form a dehydrated acidic chitosan composition;
(c) neutralizing the dehydrated, acidic chitosan composition by hydrating it in an aqueous sodium hydroxide solution;
(d) washing the chitosan composition in water to remove residual acidic and basic products;
(e) soaking the chitosan composition in an acetate buffer solution for about thirty minutes; and
(f) freezing and lyophilizing the chitosan film or sponge.
2. The method of claim 1 , wherein the buffer has a pH between 5 and 6.
3. The method of claim 1 , wherein the chitosan film or sponge is dissolved in the acid solution for a time selected from the group consisting of 1, 3, 5, 10, 15, 30, 45, 60 minutes, 3, 5, 10, and 12 hours.
4. The method of claim 1 , wherein the acid solution has a concentration between about 0.05 and 2.0 molar.
5. The method of claim 1 , wherein a 0.25 M acetate buffer is used.
6. The method of claim 1 , wherein the chitosan film or sponge degrades by at least about 20%, 30%, 40%, 50%, 60% or more in vivo in about 10-days.
7. The method of claim 1 , further comprising (g) incorporating an effective amount of at least one anti-bacterial, anti-viral, or anti-fungal agent into the chitosan composition at a point of care.
8. The method of claim 1 , wherein the chitosan film or sponge is a wound management device.
9. The method of claim 7 , wherein the agent is an antimicrobial.
10. The method of claim 1 , wherein at least about 30, 40, 50 or 60% of the chitosan film or sponge biodegrades over at least about three-five days when implanted in a subject.
11. A chitosan film or sponge produced by the method of claim 1 .
12. A wound management device comprising a chitosan film or sponge produced by the method of claim 1 .
13. The wound management device of claim 12 , wherein the chitosan film or sponge comprises an effective amount of an anti-bacterial, anti-viral, or anti-fungal agent.
14. The wound management device of claim 13 , wherein the agent is an antibiotic selected from the group consisting of daptomycin, vancomycin, and amikacin.
15. A method for treating an infection caused by Pseudomonas aeruginosa or S. aureus in a subject at a site of trauma, the method comprising contacting the site with the wound management device of claim 12 .
16. A kit comprising the wound management device of claim 12 .
17. A method for treating an infection with a Gram positive bacteria, the method comprising contacting the site with the wound management device of claim 12 .