Nanoparticles having poly(ester amide) polymer cores as drug delivery vehicles

1. A nanoparticle comprising

a core comprising a poly(ester amide) polymer comprising a repeating unit of Formula (Ia):

and a repeating unit of Formula (Ib):

wherein:

each X 1 is C 1-100 alkylene, C 2-100 alkenylene, or C 2-100 alkynylene, each of which is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of: halo, —CN, R 1 , OR 1 , NR 1 R 2 , —(C═O)R 2 , —(C═O)OR 2 , —(C═O)NR 1 R 2 , and —S(O) m R 2 ;

X 2 is C 1-100 alkylene, C 2-100 alkenylene, or C 2-100 alkynylene, each of which is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of: halo, —CN, R 1 , OR 1 , NR 1 R 2 , —(C═O)R 2 , —(C═O)OR 2 , —(C═O)NR 1 R 2 , and —S(O) m R 2 ;

X 3 is C 1-100 alkylene, C 2-100 alkenylene, or C 2-100 alkynylene, each of which is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of: halo, —CN, R 1 , OR 1 , NR 1 R 2 , —(C═O)R 2 , —(C═O)OR 2 , —(C═O)NR 1 R 2 , and —S(O) m R 2 ;

each R 1 is H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-10 aryl, 5-10-membered heteroaryl, or 4-10-membered heterocycloalkyl, each of which is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of OH, NO 2 , CN, halo, C 1-4 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, cyano-C 1-3 alkyl, HO—C 1-3 alkyl, amino, C 1-6 alkylamino, di(C 1-6 alkyl)amino, thiol, C 1-6 alkylthio, C 1-6 alkylsulfinyl, C 1-6 alkyl sulfonyl, carboxy, C 1-6 alkylcarbonyl, and C 1-6 alkoxycarbonyl;

each R 2 is H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-10 aryl, 5-10-membered heteroaryl, or 4-10-membered heterocycloalkyl, each of which is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of OH, NO 2 , CN, halo, C 1-4 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, cyano-C 1-3 alkyl, HO—C 1-3 alkyl, amino, C 1-6 alkylamino, di(C 1-6 alkyl)amino, thiol, C 1-6 alkylthio, C 1-6 alkylsulfinyl, C 1-6 alkyl sulfonyl, carboxy, C 1-6 alkylcarbonyl, and C 1-6 alkoxycarbonyl;

each m is 0, 1 or 2;

each W 1 is O, S, or NH;

each W 2 is O, S, or NH;

each A 1 is a hydrophobic aminoacid residue; and

each A 2 is a cationic aminoacid residue;

a payload molecule within the core; and

a surface layer comprising a targeting ligand that binds or reacts selectively with a receptor on the outside surface of a cell.

2. The nanoparticle of claim 1 , wherein the repeating unit of Formula (Ia) has Formula (IIa)

and

the repeating unit of Formula (Ib) has Formula (IIb):

3. The nanoparticle of claim 2 , wherein x is an integer from 2 to 10 and y is an integer from 2 to 8.

4. The nanoparticle of claim 1 , wherein A 1 is selected from the group of the following Formulae:

5. The nanoparticle of claim 1 , wherein A 2 is selected from the group of the following Formulae:

6. The nanoparticle of claim 1 , wherein the repeating unit of Formula (Ia) has Formula (IIa) or Formula (IIId):

wherein x is 4, 6 or 8 and y is 6,

and the repeating unit of Formula (Ib) has Formula (IIIb):

wherein x is 4, 6 or 8 and y is 6.

7. The nanoparticle of claim 1 , wherein the payload molecule is selected from a therapeutic protein, a chemotherapeutic agent, and an antigen.

8. The nanoparticle of claim 1 , wherein the targeting ligand that binds or reacts selectively with a receptor on the outside surface of a cell further promotes transcytosis or endocytosis of the particle.

9. A method of preparing a nanoparticle of claim 1 , the method comprising:

obtaining a first solution of the poly(ester amide) polymer comprising a repeating unit of Formula (Ia) and a repeating unit of Formula (Ib) as recited in claim 1 in a water-miscible solvent;

obtaining a second aqueous solution comprising the targeting ligand that binds or reacts selectively with a receptor on the outside surface of a cell; and

mixing the first solution with the second aqueous solution to form an aqueous suspension comprising the nanoparticle of claim 1 .

10. A composition comprising the nanoparticle of claim 1 and a pharmaceutically acceptable carrier.