Tagged poly(ester amide urethane)s, nanoparticles formed from same, and uses thereof

Patent metadata

Field	Value
Publication number	US-11090273-B2
Application number	US-201716334820-A
Country	US
Kind code	B2
Filing date	Sep 20, 2017
Priority date	Sep 20, 2016
Publication date	Aug 17, 2021
Grant date	Aug 17, 2021

Abstract

Provided are polymers (e.g., polymeric materials), nanoparticles comprising one or more of the polymers, and compositions. A polymer may be in the form of a nanoparticle. A polymer can be linear or branched. A polymer includes one or more poly(ester urea) segment, optionally, one or more poly(urethane) segment, optionally, one or more diol segment, optionally, one or more poly(ethylene glycol) segment, and, optionally, one or more terminal/end group. A polymer (e.g., a polymeric material) may include a branching moiety. For example, a composition includes one or more polymer. In an example, polymers and nanoparticles can be used to deliver a drug (e.g., gambogic acid) to an individual (e.g, who has been diagnosed with or is suspected of having cancer and/or a viral infection).

First claim

The invention claimed is:

1. A polymer comprising:
three or four polymeric groups, each polymeric group comprising:
a poly(ester urea) segment comprising one or more ester urea repeat unit with two pendant alkyl guanidinium groups;
a poly(urethane) segment comprising one or more urethane repeat unit with a pendant cross-linkable group;
a poly(ethylene glycol) segment comprising one or more ethylene glycol units;
a folate group; and
a branching moiety,

wherein in each polymeric group
the poly(ester urea) segment is covalently bonded to the poly(urethane) segment,
the poly(urethane) segment is covalently bonded to the poly(ethylene glycol) segment,
the folate group is covalently bonded a terminus of the poly(ethylene glycol) segment, and
wherein each polymeric group is covalently bonded to the branching moiety.

2. The polymer of claim 1 , wherein the poly(ester urea) segment has the following structure:

wherein
R 1 is independently, at each occurrence in the polymer, a hydrophilic group;
R 2 is, independently, at each occurrence in the polymer, a hydrophilic group;
a is independently, at each occurrence in the polymer, 1, 2, or 3; and
b is 2 or 3.

3. The polymer of claim 1 , wherein the poly(urethane) segment has the following structure:

wherein
R 3 and R 4 are independently, at each occurrence in the polymer, a side-chain comprising a cross-linkable group or hydrogen; and
e is independently, at each occurrence in the polymer, 2 or 3.

4. The polymer of claim 1 , wherein the poly(ester urea) segment has a molecular weight of 200 to 23,000 g/mol or the poly(urethane) segment has a molecular weight of 0 to 2,500 g/mol or the poly(ethylene glycol) segment has a molecular weight of 1,000 to 5,000 g/mol.

5. The polymer of claim 1 , wherein the branching moiety has the following structure:

wherein,
g is independently, at each occurrence in the polymer, 2 or 3.

6. The polymer of claim 1 , wherein the polymer has the following structure:

wherein
segment A is

segment B is

PEG is a poly(ethylene glycol) segment having a molecular weight of 1,000 to 5,000 g/mol;
folate is

m is 1 to 30; and
n is 0 to 6.

7. A polymer comprising:
a hydrophilic poly(ester urea) segment comprising one or more ester urea repeat unit having two pendant alkyl guanidinium groups;
a poly(urethane) segment comprising one or more urethane repeat unit having a pendant cross-linkable group, wherein the poly(urethane) segment has the following structure:

wherein
R 3 and R 4 are independently, at each occurrence in the polymer, a side-chain comprising a cross-linkable group or hydrogen, with the proviso that a plurality of R 3 or R 4 are a crosslinkable group; and
e is independently, at each occurrence in the polymer, 2 or 3, wherein the poly(ester urea) segment covalently bound to the poly(urethane) segment;
a first poly(ethylene glycol) segment and a second poly(ethylene glycol) segment, each segment comprising one or more ethylene glycol units; and
a first folate group and a second folate group,

wherein the first poly(ethylene glycol) segment is covalently bound to the poly(urethane) segment and the second poly(ethylene glycol) segment is covalently bound to the hydrophilic poly(ester urea) segment, and the first folate group is segment is covalently bonded to a terminus of the hydrophilic poly(ester urea) segment and the second folate group segment is covalently bonded to a terminus of the poly(urethane) segment.

8. The polymer of claim 7 , wherein the poly(ester urea) segment has the following structure:

wherein
each R 1 and each R 2 is a side chain of an arginine residue;
a is independently, at each occurrence in the polymer, 1, 2, or 3; and
b is independently, at each occurrence in the polymer, 2 or 3.

9. The polymer of claim 7 , wherein the poly(ester urea) segment has a molecular weight of 200 to 75,000 g/mol or the poly(urethane) segment has a molecular weight of 0 to 7,500 g/mol or the poly(ethylene glycol) segment has a molecular weight of 1,000 to 5,000 g/mol.

10. The polymer of claim 7 , wherein the poly(ester urea) segment is 80 to 100% of the total moles of poly(ester urea) segment and poly(urethane) segment and/or the poly(urethane) segment is 0 to 20% of the total moles of poly(ester urea) segment and poly(urethane) segment.

11. The polymer of claim 7 , wherein the polymer has the following structure:

wherein
PEG is a poly(ethylene glycol) segment having a molecular weight of 1,000 to 5,000 g/mol;
folate is

m is 1 to 70; and
n is 0 to 14.

12. A polymer comprising:
one or more hydrophilic poly(ester urea) segment, wherein the hydrophilic poly(ester urea) segment comprises the following structure:

wherein
each R 1 and R 2 are each independently, at each occurrence in the polymer, a hydrophilic group;
a is independently, at each occurrence in the polymer, 1, 2, or 3; and
b is independently, at each occurrence in the polymer, 2 or 3;
a hydrophobic poly(ester urea) segment; and
a diol segment comprising one or more diol repeat units having a pendant cross-linkable group or hydrogen, wherein the poly(ester urea) segments and diol segments are covalently bonded,

wherein the hydrophilic poly(ester urea) segment and hydrophobic poly(ester urea) segment are 80 to 100% of the total moles of the hydrophilic poly(ester urea) segment, hydrophobic (ester urea) segment, and diol segment.

13. The polymer of claim 12 , wherein the hydrophilic group is a side chain of an arginine residue.

14. The polymer of claim 12 , wherein the hydrophobic poly(ester urea) segment has the following structure:

wherein
each R 1 and R 2 are each independently, at each occurrence in the polymer, a hydrophobic group;
a is independently, at each occurrence in the polymer, 1, 2, or 3; and
b is independently, at each occurrence in the polymer, 2 or 3.

15. The polymer of claim 14 , wherein the hydrophobic group is a side chain of a leucine residue.

16. The polymer of claim 12 , wherein the diol segment

Assignees

• Univ Cornell

Inventors

• Chu Chih-Chang
• He Mingyu
• Ji Ying

Classifications

• C08G65/3332

  containing carboxamide group · CPC title

• C08G18/73 Primary

  acyclic · CPC title

• C08G18/0814

  containing ammonium groups or groups forming them · CPC title

• C08G18/3206

  aliphatic · CPC title

• C08G18/244

  tin salts of carboxylic acids · CPC title