Antimicrobial polycarbonates for multidrug resistant bacteria

Patent metadata

Field	Value
Publication number	US-10995177-B2
Application number	US-201816013474-A
Country	US
Kind code	B2
Filing date	Jun 20, 2018
Priority date	Jun 20, 2018
Publication date	May 4, 2021
Grant date	May 4, 2021

Abstract

Compositions and methods regarding guanidinium functionalized polycarbonates that provide potent antimicrobial activity against multidrug resistant (MDR) bacteria, including Klebsiella pneumoniae (K. pneumoniae) are provided. According to an embodiment, an antimicrobial guanidinium-functionalized polymer is provided that comprises a hydrophobic molecular backbone with cationic guanidinium moieties respectively bound to the hydrophobic molecular backbone via butyl spacer groups. The antimicrobial guanidinium-functionalized polymer self-assembles into a micelle structure with hydrophobic residuals of the antimicrobial guanidinium-functionalized polymer buried inside the micelle structure and the cationic guanidinium moieties exposed on an external surface of the micelle structure to target pathogens.

First claim

What is claimed is:

1. An antimicrobial guanidinium-functionalized polymer having a form of a micelle structure, the antimicrobial guanidinium-functionalized polymer, comprising:
a hydrophobic molecular backbone structure with cationic guanidinium moieties respectively bound to the hydrophobic molecular backbone structure via butyl spacer groups, wherein hydrophobic residuals of the antimicrobial guanidinium-functionalized polymer are buried inside the micelle structure and the cationic guanidinium moieties are exposed on an external surface of the micelle structure to target pathogens.

2. The antimicrobial guanidinium-functionalized polyp of claim 1 , wherein the hydrophobic molecular backbone comprises polycarbonate.

3. The antimicrobial guanidinium-functionalized polymer of claim 1 , wherein the micelle structure has a size between 20 and 300 nanometers.

4. The antimicrobial guanidinium-functionalized polymer of claim 1 , wherein the antimicrobial guanidinium-functionalized polymer self-assembles into the micelle structure in aqueous solution with a critical micelle concentration below 500 mg/L.

5. The antimicrobial guanidinium-functionalized polymer of claim 1 , wherein the micelle structure mitigates exposure of the hydrophobic residuals to mammalian cells.

6. The antimicrobial guanidinium-functionalized polymer of claim 1 , wherein the antimicrobial guanidinium-functionalized polymer is effective at killing Gram-negative bacteria and Gram-positive bacteria.

7. The antimicrobial guanidinium-functionalized polymer of claim 1 , wherein the antimicrobial guanidinium-functionalized polymer is effective at killing multidrug resistant strains of Klebsiella pneumonia.

8. The antimicrobial guanidinium-functionalized polymer of claim 1 , wherein the antimicrobial guanidinium-functionalized polymer is effective at killing bacteria selected from a group consisting of: Acinetobacter baumannii, Escherichia coli, Staphylococcus aureus , methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa and Enterococcus faccium.

9. The antimicrobial guanidinium-functionalized polymer of claim 1 , wherein the antimicrobial guanidinium-functionalized polymer has a chemical structure characterized by Structure I:

wherein n represents an integer between 5 and 65.

10. An antimicrobial polymer having a chemical structure characterized by Structure I:

wherein n represents an integer between 10 and 30, and
wherein the antimicrobial polymer has a form of a micelle with hydrophobic residuals of the antimicrobial polymer inside the micelle and hydrophilic residuals of the antimicrobial polymer on an external surface of the micelle.

11. The antimicrobial polymer of claim 10 , wherein the antimicrobial polymer has a defined balance and distribution of the hydrophobic residuals relative to the hydrophilic residuals that causes the antimicrobial polymer to self-assemble into the nanostructure in the aqueous solution.

12. The antimicrobial polymer of claim 10 , wherein the nanostructure is between 20 and 300 nanometers.

13. The antimicrobial polymer of claim 11 , wherein the antimicrobial polymer is effective at killing Gram-negative bacteria and Gram-positive bacteria.

14. The antimicrobial polymer of claim 11 , wherein the antimicrobial polymer is effective at treating lung infections caused by bacteria.

15. A method comprising:
contacting a bacteria microbe with an antimicrobial guanidinium-functionalized polymer having a form of a micelle structure in an aqueous solution, wherein the antimicrobial guanidinium-functionalized polymer comprises a hydrophobic molecular backbone structure with cationic guanidinium moieties respectively bound to the hydrophobic molecular backbone structure via butyl spacer groups, wherein hydrophobic residuals of the antimicrobial guanidium-functionalized polymer are buried inside the micelle structure and the cationic guanidinium moieties are exposed on an external surface of the micelle structure;
based on the contacting, facilitating charge naturalization of the bacterial membrane via a counterion exchange between the cationic guanidinium moieties and negatively charged phosphate groups on the bacterial membrane; and
facilitating translocation of the antimicrobial guanidinium-functionalized polymer through the bacterial membrane based on the charge neutralization.

16. The method of claim 15 , wherein the facilitating the translocation through the bacterial membrane is based on disassembling of the micelle structure and exposure of the hydrophobic residuals to the bacteria microbe in response to the contacting.

17. The method of claim 15 , wherein the hydrophobic molecular backbone structure is a polycarbonate.

18. The method of claim 15 , wherein the bacteria microbe comprises a Gram-negative bacteria microbe or a Gram-positive bacteria microbe, and Wherein the antimicrobial guanidinium-functionalized polymer is effective against lung infections caused by the bacteria microbe.

19. The antimicrobial guanidinium-functionalized polymer claim 1 , wherein the hydrophobic molecular backbone structure is a repeating structure that repeats a number of times ranging from greater than or equal to 5 and less than or equal to 65.

Assignees

• IBM
• Agency Science Tech & Res
• Coral Bay Ii Llc

Inventors

• Hedrick James L
• Yang Yi Yan
• Yang Chuan

Classifications

• C08G64/0241 Primary

  containing nitrogen · CPC title

• B82Y5/00

  Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery · CPC title

• C08G64/30

  using carbonates · CPC title

• B82Y40/00

  Manufacture or treatment of nanostructures · CPC title

• A61P31/04 Primary

  Antibacterial agents · CPC title