Telodendrimers with riboflavin moieties and nanocarriers and methods of making and using same

Abstract

Provided herein are compositions and nanocarriers comprising linear-dendritic telodendrimers (TD) containing riboflavin. The nanocarriers and compositions have desirable loading properties and stabilized structure and can be used for efficient in vivo delivery.

1 . A compound having the following structure: 
       
         
           
           
               
               
           
         
         wherein PEG is polyethylene glycol group; 
         L is optional and independently at each occurrence selected from the group consisting of 
       
       
         
           
           
               
               
           
         
         D is a dendritic polymer moiety having one or more branched monomer units selected from the group consisting of a lysine moiety, an arginine moiety, and combinations thereof; 
         R is independently at each occurrence in the compound 
       
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
       
       wherein at least one occurrence is
 m is 1; and 
 y is 4, 6, 8, 10, 12, or 16. 
 
     
     
         2 . The compound of  claim 1 , wherein the PEG group has the following structure: 
       
         
           
           
               
               
           
         
       
       wherein n is 10-500. 
     
     
         3 . The compound of  claim 1 , wherein D comprises 4 or 8 arginine moieties and each R is 
       
         
           
           
               
               
           
         
       
     
     
         4 . The compound of  claim 1 , wherein the compound is selected from the group consisting of:    
     
     
         5 . A composition comprising one or more compounds of  claim 1  and methotrexate or an anthracycline. 
     
     
         6 . The composition of  claim 5 , wherein the anthracycline is selected from the group consisting of daunorubicin, doxorubicin, epirubicin, idarubicin, and combinations thereof 
     
     
         7 . The composition of  claim 5 , wherein the one or more compounds of  claim 1  are present as a nanocarrier. 
     
     
         8 . The composition of  claim 5 , wherein for each 
       
         
           
           
               
               
           
         
       
       there is one methotrexate or anthracycline present. 
     
     
         9 . The composition of  claim 5 , wherein the composition has a nanocarrier:methotrexate/anthracycline mass ratio of 1:1 to 1:1.6. 
     
     
         10 . A method of delivering a therapeutic agent to a subject in need of treatment comprising administering to the subject an effective amount of a composition of  claim 5 . 
     
     
         11 . The method of  claim 10 , wherein the subject in need of treatment is seeking treatment from the group consisting of inflammation, autoimmune disorders, organ transplants, solid tumors, bone cancer, breast cancer, leukemia, acute lymphocytic, breast cancer, head and neck cancer, leukemia, lung cancer, lymphoma, non-Hodgkin's lymphoma, hematological cancer, cervical cancer, bladder cancer, and ovarian cancer. 
     
     
         12 . The method of  claim 10 , wherein for each 
       
         
           
           
               
               
           
         
       
       there is one methotrexate or anthracycline present. 
     
     
         13 . The method of  claim 10 , wherein the composition has a nanocarrier:methotrexate/anthracycline mass ratio of 1:1 to 1:1.6. 
     
     
         14 . The method of  claim 10 , wherein the composition of  claim 5  provides a dose of 1.5 to 3 times the recommended dose of doxorubicin or a liposomal doxorubicin formulation. 
     
     
         15 . A kit comprising:
 i) at least one compound of  claim 1  and methotrexate, an anthracycline, or a combination thereof; and   ii) a set of instructions, wherein the instructions describe how to use the compound or composition.