Cationic mucic acid polymer-based delivery system

1. A nanoparticle comprising a first polymer comprising alternating charged and uncharged segments comprising one or more of the following structural units of Formula (I) or Formula (III):

wherein

A is the uncharged segment comprising a poly-C 1-6 -alkylene glycol;

B is the charged segment comprising at least one cationic charged moiety and at least one polyhydroxy linkage comprising at least one pair of vicinal diols.

2. The nanoparticle of claim 1 , wherein A comprises polyethylene glycol and an appropriate linking group, wherein the polyethylene glycol has a nominal weight in a range of from about 1000 Daltons to about 10,000 Daltons.

3. The nanoparticle of claim 1 , where B is a cationically charged segment comprising at least one mucic acid linkage comprising the at least one pair of vicinal diols and comprising at least one repeating subunit comprising a structure of Formula (IV):

and at least one repeating subunit comprising a structure of Formula (V):

wherein m is 1, 2, 3, 4, 5, or 6.

4. The nanoparticle of claim 1 , wherein B comprises at least one repeating subunit comprising cMAP, whose subunit structure is represented as Formula (VI):

wherein

m is independently at each occurrence 4, 5, or 6; and

n is independently at each occurrence 1, 2, or 3.

5. The nanoparticle of claim 1 , described by a structure of Formula (VII):

wherein

Chain A is

Chain B is

cMAP is

p and q are sufficient to provide a number average molecular weight for the subunits comprising cMAP and PEG, respectively, independently in a range of from 1000 Da to 10,000 Da;

m is independently at each occurrence 4, 5, or 6;

n and r are independently at each occurrence 0, 1, 2, 3, 4, or 5; and

X 1 and X 2 are independently at each occurrence C 1-4 alkyl, optionally substituted with —COOH, —C(═O)O(alkyl), —NH 2 , —NH(alkyl), —N(alkyl) 2 , or a salt or protected analog thereof.

6. The nanoparticle of claim 1 , described by a structure of Formula (VII):

wherein

cMAP is

Chain B is

Chain C is

End Group D is:

p and q are sufficient to provide a number average molecular weight for the subunits comprising cMAP and PEG, respectively, independently in a range of from 1000 Da to 10,000 Da;

m is independently at each occurrence 4, 5, or 6;

n and r are independently at each occurrence 1, 2, or 3;

z is equal to or greater than 1 and up to 10; and

X 2 is independently at each occurrence C 1-6 alkyl, optionally substituted with OH, —COOH, —C(═O)O(alkyl), —NH 2 , —NH(alkyl), —N(alkyl) 2 , or a salt or protected analog thereof; and

X 3 is —NH 2 , —COOH, —C(═O)O(alkyl), or a salt or protected analog thereof.

7. The nanoparticle of claim 1 , described by a structure of Formula (IX):

wherein

End Group D is:

cMAP is

Chain C is

p and q are sufficient to provide a number average molecular weight for the subunits comprising cMAP and PEG, respectively, independently in a range of from about 500 Da to about 50,000 Da;

m is independently at each occurrence 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;

n and r are independently at each occurrence 0, 1, 2, 3, 4, or 5;

z is equal to or greater than 1 up to 10 and

X 3 and X 4 are independently at each occurrence —NH 2 , —COOH, —C(═O)O(alkyl), or a salt or protected analog thereof.

8. The nanoparticle of claim 1 , further comprising a polymer comprising a boronic acid-containing structure of Formula (X)

conjugated to the first polymer by a borate condensation linkage between the boronic acid moieties of Formula (X) and the at least one pair of vicinal diols of the polyhydroxy linkages of Formula (I) or (III), X 5 being at a distal end thereof;

R A is nitro;

n is 1;

s is 20-1200

L is —NH—C(═O)—, —C(═O)—NH—, —O—C(═O)—, or —C(═O)—O—; and

X 5 is C 1-6 alkyl, optionally substituted with —OH, —COOH, —C(═O)O(alkyl), —C(═O)O(aryl), —NH 2 , —NH(alkyl), —N(alkyl) 2 , or a salt or protected analog thereof.

9. The nanoparticle of claim 5 , further comprising a polymer comprising a boronic acid-containing structure of Formula (X)

conjugated to the first polymer by a borate condensation linkage between the boronic acid moieties of Formula (X) and the at least one pair of vicinal diols of the polyhydroxy linkages of Formula (I) or (III), X 5 being at a distal end thereof;

R A is nitro;

n is 1;

s is 20-1200

L is —NH—C(═O)—, —C(═O)—NH—, —O—C(═O)—, or —C(═O)—O—; and

X 5 is C 1-6 alkyl, optionally substituted with —OH, —COOH, —C(═O)O(alkyl), —C(═O)O(aryl), —NH 2 , —NH(alkyl), —N(alkyl) 2 , or a salt or protected analog thereof.

10. The nanoparticle of claim 6 , further comprising a polymer comprising a boronic acid-containing structure of Formula (X)

conjugated to the first polymer by a borate condensation linkage between the boronic acid moieties of Formula (X) and at the least one pair of vicinal diols of the polyhydroxy linkages of Formula (I) or (III), X 5 being at the distal end thereof;

R A is nitro;

n is 1;

s is 20-1200

L is —NH—C(═O)—, —C(═O)—NH—, —O—C(═O)—, or —C(═O)—O—; and

X 5 is C 1-6 alkyl, optionally substituted with —OH, —COOH, —C(═O)O(alkyl), —C(═O)O(aryl), —NH 2 , —NH(alkyl), —N(alkyl) 2 , or a salt or protected analog thereof.

11. The nanoparticle of claim 7 , further comprising a polymer comprising a boronic acid-containing structure of Formula (X)

conjugated to the first polymer by a borate condensation linkage between the boronic acid moieties of Formula (X) and the at least one pair of vicinal diols of the polyhydroxy linkages of Formula (I) or (III), X 5 being at a distal end thereof;

R A is nitro;

n is 1;

s is 20-1200

L is —NH—C(═O)—, —C(═O)—NH—, —O—C(═O)—, or —C(═O)—O—; and

X 5 is C 1-6 alkyl, optionally substituted with —OH, —COOH, —C(═O)O(alkyl), —C(═O)O(aryl), —NH 2 , —NH(alkyl), —N(alkyl) 2 , or a salt or protected analog thereof.

12. A plurality of nanoparticles of claim 1 , the plurality of nanoparticles being substantially monodispersed.

13. A plurality of nanoparticles of claim 8 , the plurality of nanoparticles being substantially monodispersed.

14. The nanoparticle of claim 1 , further comprising an encapsulated therapeutic agent.

15. The nanoparticle of claim 8 , further comprising an encapsulated therapeutic agent.

16. The nanoparticle of claim 1 , further comprising an encapsulated small molecule pharmaceutical, antibiotic, steroid, plasmid, peptide, peptide fragment, oligonucleotide or polynucleotide.

17. The nanoparticle of claim 8 , further comprising an encapsulated small molecule pharmaceutical, antibiotic, steroid, plasmid, peptide, peptide fragment, oligonucleotide or polynucleotide.

18. The nanoparticle of claim 14 , further comprising a conjugated targeting ligand, wherein conjugation occurs through a condensation linkage between a conjugated boronic acid-containing polymer and the targeting ligand.

19. The nanoparticle of claim 15 , further comprising a conjugated targeting ligand, wherein conjugation occurs through a condensation linkage between X 5 and the targeting ligand.

20. A pharmaceutical composition comprising a plurality of nanoparticles of claim 19 and a pharmaceutically acceptable carrier or excipient.

21. A method of improving the bioavailability of a therapeutic agent in a patient, the method comprising administering a plurality of nanoparticles of claim 19 to the patient, wherein the bioavailability of the therapeutic agent is improved relative to an administration of the therapeutic agent by itself.