Multifunctional degradable nanoparticles with control over size and functionalities

• US 9,856,348 B2
• Filed: 02/22/2016
• Issued: 01/02/2018
• Est. Priority Date: 11/05/2007
• Status: Active Grant

• Current Assignee: Vanderbilt University
• Original Assignee: Vanderbilt University
• Inventors: Harth, Eva M., Calkins, David J., Van Der Ende, Alice E.
• Primary Examiner(s): Fang, Shane
• Application Number:
  US15/049,781
• Publication Number:
  US 20160237208A1
• Time in Patent Office: 680 Days
• Field of Search: 528403, 528421, 528354, 528220, 525415
• CPC Class Codes: A61K 47/58 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
• CPC Class Codes: A61K 47/59 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
• CPC Class Codes: A61K 47/593 Polyesters, e.g. PLGA or polylactide-co-glycolide
• CPC Class Codes: A61K 47/595 Polyamides, e.g. nylon polyamino acids A61K47/62
• CPC Class Codes: A61K 49/0041 Xanthene dyes, used in vivo, e.g. administered to a mice, e.g. rhodamines, rose Bengal in vivo G01N
• CPC Class Codes: A61K 49/0056 Peptides, proteins, polyamino acids
• CPC Class Codes: A61K 49/0093 Nanoparticle, nanocapsule, nanobubble, nanosphere, nanobead, i.e. having a size or diameter smaller than 1 micrometer, e.g. polymeric nanoparticle
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/5153 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: C08G 63/08 Lactones or lactides
• CPC Class Codes: C08G 63/78 Preparation processes
• CPC Class Codes: C08G 63/912 derived from hydroxycarboxylic acids

Abstract

In one aspect, the invention relates to polymers, crosslinked polymers, functionalized polymers, nanoparticles, and functionalized nanoparticles and methods of making and using same. In one aspect, the invention relates to degradable polymers and degradable nanoparticles. In one aspect, the invention relates to methods of preparing degradable nanoparticles and, more specifically, methods of controlling particle size during the preparation of degradable nanoparticles. In one aspect, the degradable nanoparticles are useful for complexing, delivering, and releasing payloads, including pharmaceutically active payloads. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Claims

1. A polymer comprising at least one propargyl-functionalized monomer residue having an optionally substituted structure represented by a formula:

2. The polymer of claim 1, wherein at least one propargyl-functionalized monomer provides the at least one propargyl-functionalized monomer residue and has an optionally substituted structure represented by a formula:

3. The polymer of claim 2, wherein the at least one propargyl-functionalized monomer has the optionally substituted structure represented by the formula:

4. The polymer of claim 1, further comprising:

at least one monomer residue having an optionally substituted structure represented by a formula;

5. The polymer of claim 2, wherein at least one monomer provides the at least one monomer residue and has an optionally substituted structure represented by a formula:

6. The polymer of claim 5, wherein the at least one monomer has the optionally substituted structure represented by the formula:

7. The polymer of claim 1, further comprising:

at least one keto-functionalized monomer residue having an optionally substituted structure represented by a formula;

8. The polymer of claim 7, wherein at least one keto-functionalized monomer provides the at least one keto-functionalized monomer residue and has an optionally substituted structure represented by a formula:

9. The polymer of claim 8, wherein the at least one keto-functionalized monomer has an optionally substituted structure represented by a formula:

10. The polymer of claim 1, further comprising:

at least one alkene-functionalized monomer residue having an optionally substituted structure represented by a formula;

11. The polymer of claim 10, wherein at least one alkene-functionalized monomer provides the at least one alkene-functionalized monomer residue and has an optionally substituted structure represented by a formula:

12. The polymer of claim 11, wherein the at least one alkene-functionalized monomer has the optionally substituted structure represented by the formula:

13. The polymer of claim 1, further comprising:

at least one epoxide-functionalized monomer residue having an optionally substituted structure represented by a formula;

14. A polymer produced by a method comprising a step of copolymerizing a mixture of:

a. at least one propargyl-functionalized monomer residue having an optionally substituted structure represented by a formula;

15. The method of claim 14, wherein the at least one alkene-functionalized monomer residue is present and the method further comprises a step of oxidizing the resultant polymer to provide an epoxide-functionalized monomer residue having an optionally substituted structure represented by a formula:

16. The method of claim 15, further comprising the step of functionalizing the polymer, wherein functionalizing the polymer comprises the step of reacting:

a. the at least one epoxide-functionalized monomer residue having the optionally substituted structure represented by the formula;

17. The method of claim 14, the method further comprising a step of functionalizing the polymer.

18. The method of claim 17, wherein functionalizing the polymer comprises the step of reacting:

a. the propargyl-functionalized monomer residue having the optionally substituted structure represented by the formula;

19. The method of claim 17, wherein the at least one keto-functionalized monomer residue is present and functionalizing comprises a step of reacting:

a. the keto-functionalized monomer residue having an optionally substituted structure represented by a formula;

20. A polymer comprising at least one alkene-functionalized monomer residue having an optionally substituted structure represented by a formula:

21. The polymer of claim 20, wherein at least one alkene-functionalized monomer provides the at least one alkene-functionalized monomer residue and has an optionally substituted structure represented by a formula:

22. The polymer of claim 21, wherein the at least one alkene-functionalized monomer has the optionally substituted structure represented by the formula:

23. The polymer of claim 20, further comprising:

at least one monomer residue having an optionally substituted structure represented by a formula;

24. The polymer of claim 23, wherein at least one monomer provides the at least one monomer residue and has an optionally substituted structure represented by a formula:

25. The polymer of claim 24, wherein the monomer has the optionally substituted structure represented by the formula:

26. The polymer of claim 20, further comprising:

at least one keto-functionalized monomer residue having an optionally substituted structure represented by a formula;

27. The polymer of claim 26, wherein at least one keto-functionalized monomer provides the at least one keto-functionalized monomer residue and has an optionally substituted structure represented by a formula:

28. The polymer of claim 27, wherein the at least one keto-functionalized monomer has an optionally substituted structure represented by a formula:

29. The polymer of claim 20, further comprising:

at least one epoxide-functionalized monomer residue having an optionally substituted structure represented by a formula;

30. A polymer produced by a method comprising a step of copolymerizing a mixture of:

a. at least one alkene-functionalized monomer providing a residue having an optionally substituted structure represented by a formula;

31. The method of claim 30, wherein the at least one alkene-functionalized monomer residue is present and the method further comprises the step of oxidizing the resultant polymer to provide an epoxide-functionalized monomer residue having an optionally substituted structure represented by a formula:

32. The method of claim 31, further comprising a step of functionalizing the polymer, wherein functionalizing the polymer comprises the step of reacting:

a. the at least one epoxide-functionalized monomer residue having the optionally substituted structure represented by the formula;

33. The method of claim 30, the method further comprising a step of functionalizing the polymer.

34. The method of claim 33, wherein the at least one keto-functionalized monomer residue is present and functionalizing the polymer comprises the step of reacting:

a. the keto-functionalized monomer residue having an optionally substituted structure represented by a formula;