Multifunctional degradable nanoparticles with control over size and functionalities

• US 7,935,782 B2
• Filed: 11/05/2008
• Issued: 05/03/2011
• Est. Priority Date: 11/05/2007
• Status: Active Grant

• Current Assignee: Vanderbilt University
• Original Assignee: Vanderbilt University
• Inventors: Hamilton, Sharon K., Harth, Eva M., Croce, Teresa A., Van Der Ende, Alice E.
• Primary Examiner(s): Gulakowski; Randy
• Assistant Examiner(s): Fang; Shane
• Application Number:
  US12/265,701
• Publication Number:
  US 20090306335A1
• Time in Patent Office: 909 Days
• Field of Search: 528/403
• US Class Current: 528/403
• CPC Class Codes: A61K 47/6935 the polymer being obtained otherwise than by reactions involving carbon to carbon unsaturated bonds, e.g. polyesters, polyamides or polyglycerol
• CPC Class Codes: A61K 49/0043 Fluorescein, used in vivo
• CPC Class Codes: A61K 49/0054 Macromolecular compounds, i.e. oligomers, polymers, dendrimers
• CPC Class Codes: A61K 49/0067 quantum dots, fluorescent nanocrystals
• 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: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C08G 63/06 derived from hydroxycarboxylic acids
• CPC Class Codes: C08G 63/912 derived from hydroxycarboxylic acids
• CPC Class Codes: C08G 71/02 Polyureas
• CPC Class Codes: C08J 2300/16 Biodegradable polymers
• CPC Class Codes: C08J 3/12 Powdering or granulating
• CPC Class Codes: C08J 3/14 by precipitation from solutions C08J3/122 takes precedence

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 polymer 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 method of preparing a degradable nanoparticle comprising the step of reacting a polymer comprising at least one monomer residue having a structure represented by a formula:

2. The method of claim 1, wherein reacting is adding a polymer comprising at least one monomer residue having a structure represented by a formula:

3. The method of claim 1, wherein reacting is contacting a polymer comprising at least one monomer residue having a structure represented by a formula:

4. The method of claim 3, wherein the solution comprises from about 1 molar equivalent of a dinucleophile and the resultant nanoparticle has a particle size of from about 5 nm to about 55 nm.

5. The method of claim 3, wherein the solution comprises from about 2 molar equivalents of a dinucleophile and the resultant nanoparticle has a particle size of from about 30 nm to about 80 nm.

6. The method of claim 3, wherein the solution comprises from about 3 molar equivalents of a dinucleophile and the resultant nanoparticle has a particle size of from about 70 nm to about 13 nm.

7. The method of claim 3, wherein the solution comprises from about 4 molar equivalents of a dinucleophile and the resultant nanoparticle has a particle size of from about 110 nm to about 170 nm.

8. The method of claim 3, wherein the solution comprises from about 5 molar equivalents of a dinucleophile and the resultant nanoparticle has a particle size of from about 175 nm to about 300 nm.

9. The method of claim 3, wherein the solution comprises from about 6 molar equivalents of a dinucleophile and the resultant nanoparticle has a particle size of from about 250 nm to about 350 nm.

10. The method of claim 3, wherein the solution comprises from about 8 molar equivalents of a dinucleophile and the resultant nanoparticle has a particle size of from about 400 nm to about 550 nm.

11. The method of claim 3, wherein the solution comprises from about 10 molar equivalents of a dinucleophile and the resultant nanoparticle has a particle size of from about 650 nm to about 850 nm.

12. The method of claim 1, wherein the monomer residue comprises less than about 10% by weight of the monomer residue of halogen selected from chlorine, bromine, and iodine.

13. The method of claim 1, wherein Z is O.

14. The method of claim 1, wherein the nanoparticle is further substituted with at least one biologically active agent, at least one pharmaceutically active agent, and/or at least one imaging moiety.

15. The method of claim 1, further comprising the step of administering to a subject an effective amount of the degradable nanoparticle, wherein the nanoparticle is further substituted with at least one biologically active agent, at least one pharmaceutically active agent, and/or at least one imaging moiety.

16. The method of claim 1, wherein the nanoparticle has at least one epoxide-functionalized monomer residue, the method further comprising the step of reacting the nanoparticle with a nucleophile having a structure represented by a formula X—

R¹,

wherein X is OH, SH, NH₂, or NHR, wherein R is H or C1 to C6 alkyl; and

wherein R¹ is an optionally substituted organic radical comprising 1 to 24 carbon atoms, thereby functionalizing the nanoparticle.

17. The method of claim 16, wherein Z is O.

18. The method of claim 17, wherein X is NH₂ or NHR.

19. The method of claim 17, R¹ is further substituted with at least one biologically active agent, at least one pharmaceutically active agent, and/or at least one imaging moiety.