Therapeutic and vaccine polyelectrolyte nanoparticle compositions

Abstract

Polyelectrolyte nanoparticle compositions for biomedical applications are provided comprising at least two carrier domains comprising multivalent ionic domains and an agent exhibiting biological activity when contained within the nanoparticle or on the nanoparticle surface. The multivalent ionic domains may be contained in two separate molecules or in separate but linked domains of a single molecule. The nanoparticle optionally can further comprise an exposed targeting ligand and/or protective surface. The nanoparticle can be contacted to cells or administered directly to an animal for biomedical applications including therapeutics and immune response. The nanoparticle may alternatively be comprised of a carrier material capable of delivering various medically important antigens as vaccine.

1 . A nanoparticle comprising:
 a first polyvalent carrier domain wherein the first polyvalent carrier domain is made up of more positively ionizable moieties than negatively ionizable moieties,   a second polyvalent carrier domain wherein the second polyvalent carrier domain is made up of more negatively ionizable moieties than positively ionizable moieties,   and an ionizable biologically active agent associated with the carrier.   
     
     
         2 . The nanoparticle of  claim 1  wherein the first and second polyvalent carrier domains are attached covalently to one another thereby providing both domains in the same molecule. 
     
     
         3 . The nanoparticle of  claim 1  wherein the first and second polyvalent carrier domains are present on two separate molecules. 
     
     
         4 - 7 . (canceled) 
     
     
         8 . The nanoparticle of  claim 1  wherein the first or second polyvalent carrier domain comprises a polymer selected from the group consisting of a polyamide, a polysaccharide, a polyacetal, and a polyester. 
     
     
         9 . The nanoparticle of  claim 1  wherein the first or second polyvalent carrier domain comprises multivalent cationic ionizable moieties selected from the group consisting of a polyamine, a polyallylamine, a polyimine, a polyethyleneimine, a cationic functionalized polyester, a cationic functionalized polyamide backbone, a cationic polypeptide, a polylysine, an imidazole a derivatized polylysine, a histidinelysine copolymer, and an aminodextran. 
     
     
         10 . (canceled) 
     
     
         11 . The nanoparticle of  claim 1  wherein the first or second polyvalent carrier domain comprises at least about 10% monomers capable of forming a branch. 
     
     
         12 . The nanoparticle of  claim 1  wherein the first or second polyvalent carrier domain comprises a substantially random branched polyamide. 
     
     
         13 . (canceled) 
     
     
         14 . The nanoparticle of  claim 1  wherein the first or second carrier domain comprises a cationic polyamide comprising a) at least about 20% monomer carrying an amine moiety, b) less than about 5% monomer carrying a guanidinium moiety, and c) less than about 5% monomer carrying an anionic moiety. 
     
     
         15 . The nanoparticle of  claim 14  wherein the polymer further comprises at least about 40% monomer carrying an imidazole moiety. 
     
     
         16 . The nanoparticle of claim  7  wherein the polysaccharide is selected from the group consisting of a dextran sulfate, chitin, and hyaluronic acid. 
     
     
         17 . (canceled) 
     
     
         18 . The nanoparticle of claim  7  wherein the polyester is selected from the group consisting of a polyserine, a polythreonine, dextran sulfate, chitin, and hyaluronic acid. 
     
     
         19 . The nanoparticle of  claim 1  wherein the ionizable biologically active agent comprises an antigen. 
     
     
         20 . The nanoparticle of  claim 1  wherein the nanoparticle comprises the anthrax protective antigen binding domain for an antigen presenting cell. 
     
     
         21 . The nanoparticle of  claim 19  wherein the antigen comprises an antigenic component of an infectious organism. 
     
     
         22 . The nanoparticle of  claim 1  wherein the particle includes poly-gamma-D-glutamic acid of at least 3 monomers in length as part of the first or second polyvalent carrier domain or as the biologically active agent. 
     
     
         23 . The nanoparticle of  claim 21  wherein the antigen comprises an antigenic sequence of anthrax protective antigen. 
     
     
         24 . The nanoparticle of  claim 25  further comprising a second antigen comprising poly-gamma-D-glutamic acid of at least 3 monomers in length and wherein the composition lacks exposed polyglutamic acid. 
     
     
         25 . The nanoparticle according to  claim 1  wherein the biologically active agent is Squalamine, PGA polymer 
     
     
         26 . The nanoparticle according to  claim 1  wherein the nanoparticle is provided in a pharmaceutically acceptable formulation. 
     
     
         27 . A method for modifying the metabolism of an organism, comprising administering the nanoparticle according to  claim 1  to the organism thereby treating the disease state in the organism.