Biodegradable targetable microparticle delivery system

Abstract

Copolymers designed for use as particulate carriers containing functionalizable amino acid subunits for coupling with targeting ligands are described. The copolymers are polyesters composed of α-hydroxy acid subunits such as D,L-lactide and pseudo-α-amino acid subunits which may be derived from serine or terpolymers of D,L-lactide and glycolide and pseudo-α-amino acid subunits which may be derived from serine. Stable vaccine preparations useful as delayed release formulations containing antigen or antigens and adjuvants encapsulated within or physically mixed with polymeric microparticles are described. The particulate carriers are useful for delivering agents to the immune system of a subject by mucosal or parenteral routes to produce immune responses, including antibody and protective responses.

1 - 70 . (canceled)  
     
     
         71 . An immunogenic composition comprising a particulate carrier for delivery of biologically active material to a host, an immunogen and a physiologically acceptable carrier thereof, said carrier comprising a polymer having a molecular weight of about 5000 to about 40,000 daltons and having the general formula:  
       wherein: 
 R 1 , R 2  and R 4  are selected independently and are selected from H 1 , linear or  
                     
 branched alkyl groups;  
 R 3  and R 4  are H;  
 R 6  is selected from H, an amine protecting group, a spacer molecule or a biologically active species;  
 X is selected from an O or S group; and  
 x and y are integers.  
 
     
     
         72 . A method of producing an immune response in a host comprising administering the immunogenic composition of  claim 71  to said host.  
     
     
         73 . The method of  claim 72 , wherein said composition is administered mucosally or parenterally.  
     
     
         74 . The method of  claim 72 , wherein said immune response is an antibody response.  
     
     
         75 . The method of  claim 74 , wherein said antibody response is a local or serum antibody response.  
     
     
         76 . The immunogenic composition of  claim 71  wherein said particulate carrier has a particle size of about 1 to 10 μm.  
     
     
         77 . The composition of  claim 71 , wherein said polymer is derived by copolymerization of monomers comprising at least one α-hydroxy acid and at least one pseudo-α-amino acid.  
     
     
         78 . The composition of  claim 77 , wherein the at least one α-hydroxy acid has the formula of R 1 R 2 COHCO 2 H, wherein the R 1  and R 2  groups are H, linear or branched alkyl units, the alkyl unit being represented by the formula C n H 2n+1 , where n=integer of about 1 to 10.  
     
     
         79 . The composition of clam 78, wherein said α-hydroxy acids comprise a mixture of α-hyrdroxy acids, one of said mixture of α-hyrdoxy acids having R 1  and R 2  groups which are hydrogen and the other of said mixture of α-hydroxy acids having an R 1  group which is CH 3  and R 2  group which is H.  
     
     
         80 . The composition of  claim 77 , wherein the at least one pseudo-α-hydroxy acids has the formula R 5 CHNHR 6 CO 2 H, wherein the R 5  group is a hydroxylmethyl or methyl thiol group and R 6  is an amine protecting group.  
     
     
         81 . The composition of  claim 80 , wherein the amine protecting group is selected from the group consisting of carbobenzyloxy (CBZ or Z)m benzyl (Bn)m paramethoxybenzyl (MeOBn), benzyloxymethoxy (BOM), tert-butyloxycarbonyl (t-BOC) and [9-fluorenylmethyl oxy]carbonyl (FMOC).  
     
     
         82 . The composition of  claim 77 , wherein the at least one α-hydroxy acid is selected from the group consisting of L-lactic acid, D,L-lactic acid, glycolic acid, hydroxy valeric acid and hydroxybutyric acid.  
     
     
         83 . The composition of  claim 77 , wherein the at least one pseudo-α-amino acid is derived from serine.  
     
     
         84 . The composition of  claim 71 , wherein said at least one α-hydroxy acid monomer and at least one pseudo-α-amino acid monomer are selected to result in poly-D, L-lactide-co-glycolide-co-pseudo-Z-serine ester (PLGpZS).  
     
     
         85 . The composition of  claim 71 , wherein said at least one α-hydroxy acid monomer and at least one pseudo-α-amino acid monomer are selected to result in poly-D, L-lactide-co-glycolide-co-pseudo-serine ester (PLGpS).  
     
     
         86 . The composition of  claim 71 , wherein R 6  is at least one biologically active species.