Compositions and methods of use thereof
Described herein are methods for treating or preventing a disease or disorder of the pulmonary system (e.g., cystic fibrosis), respiratory or digestive system in a subject, the methods comprising administering compounds or compositions comprising water soluble polyglucosamine and derivatized polyglucosamine.
1. A method for treating or preventing Acute Respiratory Distress Syndrome (ARDS) in a subject, the method comprising administering to the subject by inhalation an effective amount of a composition comprising a neutral osmol agent and a poly (acetyl, arginyl) glucosamine (PAAG) comprising the following formula (I):
wherein:
n is an integer between 20 and 6000; and
each R 1 is independently selected for each occurrence from hydrogen, acetyl,
wherein at least 25% of R 1 substituents are H, at least 1% of R 1 substituents are acetyl, and at least 2% of R 1 substituents are
wherein the osmolality of the composition is between 150-550 mOsmol/kg; and
wherein the neutral osmol agent is selected from the group consisting of glycerol, sorbitol, mannitol, xylitol, erythritol, and trehalose.
2. The method of claim 1 , wherein the subject has pneumonia.
3. The method of claim 1 , wherein the subject has cystic fibrosis (CF), chronic pulmonary disorder (COPD), primary ciliary dyskinesia, or non-CF bronchiectasis.
4. The method of claim 1 , wherein the method reduces bacterial or biofilm cohesion.
5. The method of claim 1 , wherein the method increases mucociliary clearance.
6. The method of claim 1 , wherein the concentration of PAAG that is administered to the subject is from about 50 μg/mL to about 600 μg/mL.
7. The method of claim 1 , wherein the concentration of PAAG that is administered to the subject is about 250 μg/mL.
8. The method of claim 1 , wherein the average molecular weight of the PAAG is from about 70 to about 120 kDa.
9. The method of claim 1 , wherein the polydispersity index of the PAAG is from 1.0 to 2.5.
10. The method of claim 1 , wherein the PAAG is arginine-functionalized at least 18%.
11. The method of claim 1 , wherein the PAAG is arginine-functionalized at between 20%-30%.
12. The method of claim 1 , wherein the PAAG is greater than 18% arginine-functionalized.
13. The method of claim 1 , wherein the PAAG is present in the composition at between 0.1-2 mg/ml.
14. The method of claim 1 , the method further comprising administering a nebulizer solution composition configured for inhaled administration.
15. The method of claim 1 , wherein the composition is administered in an amount sufficient to provide about 0.2 mg to about 3 mg of PAAG to the subject.
16. The method of claim 1 , the method further comprising administering an antibacterial agent.
17. The method of claim 1 , wherein the neutral osmol agent is glycerol.
18. The method of claim 17 , wherein the glycerol is present in the composition at between 1.2-1.6% v/v.
19. The method of claim 1 , wherein the neutral osmol agent is trehalose.