Methods and compositions for disrupting biofilm utilizing chitosan-derivative compounds

Abstract

Described herein are methods of disrupting (e.g., reducing the viscosity of, or dissolving) a preformed biofilm in a subject, the method comprising: administering to the subject an effective amount of a composition comprising a soluble chitosan or derivatized chitosan wherein the soluble chitosan or derivatized chitosan when administered contacts the preformed biofilm, thereby disrupting (e.g., reducing the viscosity of, or dissolving) the preformed biofilm.

1 - 93 . (canceled) 
     
     
         94 . A method of treating or preventing a complication of cystic fibrosis in a subject, the method comprising:
 administering to the subject an effective amount of a composition comprising a soluble chitosan or derivatized chitosan, wherein the derivatized chitosan comprises a chitosan of 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, and a group of formula (II): wherein, formula (II) is selected from 
       
         
           
           
               
               
           
         
         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 a group of formula (II), 
       
       thereby treating a complication of cystic fibrosis. 
     
     
         95 - 104 . (canceled) 
     
     
         105 . A nebulizer comprising a solution or powder of soluble derivatized chitosan, wherein the derivatized chitosan comprises a chitosan of 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, and a group of formula (II): wherein, formula (II) is selected from 
       
         
           
           
               
               
           
         
         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 a group of formula (II). 
       
     
     
         106 - 111 . (canceled) 
     
     
         112 . The method of  claim 94 , wherein the method comprises reducing the viscosity of a biofilm in the subject. 
     
     
         113 . The method of  claim 112 , wherein the biofilm is in the respiratory system. 
     
     
         114 . The method of  claim 94 , wherein the method comprises reducing the viscosity of viscous sputum associated with cystic fibrosis. 
     
     
         115 . The method of  claim 94 , wherein the method comprises increasing the pourability of sputum compared to the sputum that has not been contacted with the composition. 
     
     
         116 . The method of  claim 112 , wherein the method comprises reducing the viscosity of the biofilm by at least 50% compared to the biofilm that has not been contacted with the composition. 
     
     
         117 . The method of  claim 112 , wherein the method comprises partially dissolving the biofilm compared to the biofilm that has not been contacted with the composition. 
     
     
         118 . The method of  claim 94 , further comprising administering an additional agent. 
     
     
         119 . The method of  claim 118 , wherein the additional agent is administered in a dosage to achieve a synergistic effect. 
     
     
         120 . The method of  claim 118 , wherein the additional agent is administered together with the soluble derivatized chitosan. 
     
     
         121 . The method of  claim 94 , further comprising administering an antibiotic, anti-inflammatory, or mucolytic compound to a subject in conjunction with, prior to, or subsequent to the administration of the composition. 
     
     
         122 . The method of  claim 121 , wherein the antibiotic, anti-inflammatory, or mucolytic compound is administered in a dosage to achieve a synergistic effect. 
     
     
         123 . The method of  claim 94 , wherein the composition is administered by inhalation. 
     
     
         124 . The method of  claim 94 , wherein the effective amount is a therapeutically effective amount. 
     
     
         125 . The method of  claim 124 , wherein the therapeutically effective amount is from about 10 to 250 μg/mL. 
     
     
         126 . The method of  claim 94 , wherein the subject is infected with bacteria listed in Table 1, 2, 3, or 4. 
     
     
         127 . The method of  claim 94 , wherein the derivatized chitosan is soluble in aqueous solution from about pH 6.8 to about pH 9. 
     
     
         128 . The method of  claim 94 , wherein the molecular weight of the derivatized chitosan is between 10,000 and 100,000 Da. 
     
     
         129 . The method of  claim 94 , wherein the chitosan is functionalized at between 20% and 30%. 
     
     
         130 . The method of  claim 94 , wherein the degree of deacetylation (% DDA) of the derivatized chitosan is between 75% and 95%. 
     
     
         131 . The method of  claim 94 , wherein the polydispersity index (PDI) of the derivatized chitosan is between 1.0 and 2.5.