Poly(beta-amino alcohols), their preparation, and uses thereof

Abstract

A new class of poly(beta-amino alcohols) (PBAAs) has been prepared using combinatorial polymerization. The inventive PBAAs may be used in biotechnology and biomedical applications as coatings (such as coatings of films or multilayer films for medical devices or implants), additives, materials, excipients, non-biofouling agents, micropatterning agents, and cellular encapsulation agents. When used as surface coatings, these PBAAs elicited different levels of inflammation, both in vitro and in vivo, depending on their chemical structures. The large chemical diversity of this class of materials allowed us to identify polymer coatings that inhibit macrophage activation in vitro. Furthermore, these coatings reduce the recruitment of inflammatory cells, and reduce fibrosis, following the subcutaneous implantation of carboxylated polystyrene microparticles. These polymers may be used to form polyelectrolyte complex capsules for cell encapsulation. The invention may also have many other biological applications such as antimicrobial coatings, DNA or siRNA delivery, and stem cell tissue engineering.

What is claimed is: 
     
         1 . A polymer of formula: 
       
         
           
           
               
               
           
         
       
       wherein:
 each A and B is, independently, a bond; a substituted or unsubstituted, branched or unbranched, cyclic or acyclic C 1-20  aliphatic; a substituted or unsubstituted, branched or unbranched, cyclic or acyclic C 1-20  heteroaliphatic; substituted or unsubstituted aryl; or a substituted or unsubstituted heteroaryl; 
 each R 1  and R 2  is, independently, unsubstituted, branched or unbranched, cyclic or acyclic C 1-20  aliphatic; substituted or unsubstituted aryl; or a substituted or unsubstituted heteroaryl; 
 each 
 
       
         
           
           
               
               
           
         
       
       may optionally form a cyclic structure by the joining of R 1  and R 2 ;
 each R 3 , R 4 , and R 5  is hydrogen; a substituted or unsubstituted, branched or unbranched, cyclic or acyclic C 1-20  aliphatic; a substituted or unsubstituted, branched or unbranched, cyclic or acyclic C 1-20  heteroaliphatic; a substituted or unsubstituted aryl; or a substituted or unsubstituted heteroaryl; 
 each 
 
       
         
           
           
               
               
           
         
       
       may optionally form a cyclic structure;
 each E and G is, independently, hydrogen; a substituted or unsubstituted, branched or unbranched, cyclic or acyclic C 1-20  aliphatic; a substituted or unsubstituted, branched or unbranched, cyclic or acyclic C 1-20  heteroaliphatic; substituted or unsubstituted aryl; a substituted or unsubstituted heteroaryl; 
 
       
         
           
           
               
               
           
         
       
       n is an integer from 2 to 10,000, inclusive; or a salt thereof. 
     
     
         2 . The polymer of  claim 1 , wherein A is substituted or unsubstituted, branched or unbranched, cyclic or acyclic C 1-20  aliphatic, or substituted or unsubstituted, branched or unbranched, cyclic or acyclic C 1-20  heteroaliphatic. 
     
     
         3 . The polymer of  claim 1 , wherein A is substituted or unsubstituted, branched or unbranched, cyclic or acyclic C 1-20  alkylene. 
     
     
         4 . The polymer of  claim 1 , wherein A is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       wherein:
 each R 10  is, independently, hydrogen; a substituted or unsubstituted, branched or unbranched, cyclic or acyclic C 1-20  aliphatic; a substituted or unsubstituted, branched or unbranched, cyclic or acyclic C 1-20  heteroaliphatic; substituted or unsubstituted aryl; a substituted or unsubstituted heteroaryl; or an N-protecting group; and 
 each q is, independently, an integer between 0 and 10, inclusive. 
 
     
     
         5 . The polymer of  claim 1 , wherein 
       
         
           
           
               
               
           
         
       
       is selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         6 . The polymer of  claim 1 , wherein B is substituted or unsubstituted, branched or unbranched, cyclic or acyclic C 1-20  aliphatic, or substituted or unsubstituted, branched or unbranched, cyclic or acyclic C 1-20  heteroaliphatic. 
     
     
         7 . The polymer of  claim 1 , wherein B is substituted or unsubstituted, branched or unbranched, cyclic or acyclic C 1-20  alkylene. 
     
     
         8 . The polymer of  claim 1 , wherein B is selected from the group consisting of:
 a bond,   
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       wherein each q is, independently, an integer between 0 and 10, inclusive. 
     
     
         9 . The polymer of  claim 1 , wherein each R 1  and R 2  is independently unsubstituted, branched or unbranched, cyclic or acyclic C 1-20  aliphatic. 
     
     
         10 . The polymer of  claim 1 , wherein each R 1  and R 2  is independently a substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl. 
     
     
         11 . The polymer of  claim 1 , wherein R 1  and R 2  are all unsubstituted C 1 -C 6  alkyl. 
     
     
         12 . The polymer of  claim 1 , wherein each R 1  and R 2  is independently selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         13 . The polymer of  claim 1 , wherein all R 3 , R 4 , and R 5  are hydrogen. 
     
     
         14 . The polymer of  claim 1 , wherein each R 3 , R 4 , and R 5  is independently selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         15 . The polymer of  claim 1 , wherein the weight-average molecular weight as determined by gel permeation chromatography ranges between 1,000 and 100,000 Daltons. 
     
     
         16 . A polymer prepared by reacting:
 an epoxide selected from the group consisting of:   
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       wherein each q is, independently, an integer between 0 and 10, inclusive; and
 an amine selected from the group consisting of: 
 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         17 . The polymer of  claim 16 , selected from the group consisting of: F18, C01, F28, E19, B20, D19, A03, A01, F12, A28, B19, A19, B01, A20, F19, F10, F20, B12, A10, and A12. 
     
     
         18 . A pharmaceutical composition comprising a polymer of  claim 1 ; and a pharmaceutical agent. 
     
     
         19 . A liposome, microparticle, or micelle, each of which comprises a polymer of  claim 1 ; and an agent to be delivered. 
     
     
         20 . A medical device or implant, each of which is coated with a polymer of  claim 1 . 
     
     
         21 . A surface coated with a polymer of  claim 1 . 
     
     
         22 . A complex comprising a polymer of  claim 1 ; and a polynucleotide. 
     
     
         23 . A method of administering an agent, the method comprising the step of administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising: a polymer of  claim 1  and an agent to be delivered.