Synthesis of novel poly(ester urea)s for drug delivery

1 . A poly(ester urea) comprising two or more units having a structure:

[(AA1) p -linker-(AA2) q ]  Formula I

wherein:

at least two units are covalently bonded via a urea bond;

each of AA1 and AA2 is independently an unprotected or protected amino acid monomer;

p and q are independently 1 or 2; and

wherein the linker is a branched chemical moiety consisting of a structure selected from:

 and a combination thereof, wherein each Z, Z′, Z″, Z′″, and Z″″ is independently O, S, or NRy, wherein Ry is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, and each n1, n2, n3, n4, and n5 is independently an integer between 1 and 20.

2 . The poly(ester urea) of claim 1 , comprising a structure:

[(AA1)-linker-(AA2)] n   Formula II

wherein n is an integer greater than 2 and less than 1000.

3 . The poly(ester urea) of claim 1 , wherein the amino acid monomers comprise a cationic amino acid monomer, an anionic amino acid monomer, an aromatic amino acid monomer, or a side chain protected derivative thereof.

4 . The poly(ester urea) of claim 1 , wherein the amino acid monomers comprise a cationic amino acid monomer, an anionic amino acid monomer, or a side chain protected derivative thereof.

5 . The poly(ester urea) of claim 1 , wherein the amino acid monomers comprise a cationic amino acid monomer or a side chain protected derivative thereof.

6 . The poly(ester urea) of claim 1 , wherein the amino acid monomers comprise an anionic amino acid monomer or a side chain protected derivative thereof.

7 . The poly(ester urea) of claim 1 , wherein the amino acid monomers comprise an aromatic amino acid monomer or a side chain protected derivative thereof.

8 . The poly(ester urea) of claim 1 , wherein the amino acid monomers are selected from lysine, arginine, ornithine, histidine, aspartic acid, glutamic acid, phenylalanine, tyrosine, or a side chain protected derivative thereof.

9 . The poly(ester urea) of claim 3 , wherein the side chain protected derivative contains a protecting moiety selected from benzyloxycarbonyl, benzyl, allyloxycarbonyl, 9-fluorenylmethoxycarbonyl, tert-butyloxycarbonyl, tert-butyl, trityl, 2,4-dimethoxybenzyl, 9-fluorenylmethyl, 2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran-5-sulfonyl, 9-xanthenyl, tosyl, benzyloxymethyl, formyl, tert-butyldimethylsilyl, allyl, o-nitrobenzyl, acetamidomethyl.

10 . The poly(ester urea) of claim 3 , wherein the side chain protected derivative contains a protecting moiety selected from benzyloxycarbonyl or benzyl.

11 . The poly(ester urea) of claim 1 , wherein the linker is a branched chemical moiety consisting of a structure selected from:

and a combination thereof, wherein n1, n2, n3, n4, and n5 are 2.

12 . A polyplex comprising the poly(ester urea) of claim 1 and one or more therapeutic, prophylactic, or diagnostic agents.

13 . The polyplex of claim 12 , comprising a polyelectrolyte complex of the poly(ester urea) and the one or more therapeutic, prophylactic, or diagnostic agents.

14 . The polyplex of claim 12 , in the form of a micelle, a liquid polyplex, or a thin-film coating.

15 . A pharmaceutical composition comprising the polyplex of claim 12 and a pharmaceutically acceptable carrier.

16 . A method of administering one or more therapeutic, prophylactic, or diagnostic agents to a subject in need thereof, the method comprising injecting or transplanting the polyplex of claim 12 to the subject.

17 . A poly(ester urea), having a structure selected from:

and combinations thereof,

wherein n is greater than 2 and less than 1000

wherein each of the poly(ester urea) has at least two structures recited above covalently bonded via a urea bond.