Linear Polyester and Semi-Linear Glycidol Polymer Systems: Formulation and Synthesis of Novel Monomers and Macromolecular Structures

Patent metadata

Field	Value
Publication number	US-2016206743-A1
Application number	US-201514918115-A
Country	US
Kind code	A1
Filing date	Oct 20, 2015
Priority date	Jun 15, 2012
Publication date	Jul 21, 2016
Grant date	—

Abstract

Disclosed herein are glycidol-based polymers, nanoparticles, and methods related thereto useful for drug delivery. 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.

First claim

What is claimed is:

1 . A polymer comprising repeating units selected from:

wherein R 0 is selected from H, alkyl, NH 2 , and R 1 ;
wherein R 1 comprises a crosslinking functionality;
wherein repeating units A1, A2, B1, and B2 account for at least about 50 wgt % of the polymer; and
wherein the ratio of (A1+A2):(B1+B2) is greater than 1.

2 . The polymer of claim 1 , further comprising at least one repeating unit formed from a monomer selected from:

or a combination thereof.

3 . The polymer of claim 2 , wherein the polymer comprises at least one repeating unit from a monomer selected from:

or a combination thereof,
and wherein the polymer is oxidized to form repeating units comprising epoxides or alkynes.

4 . The polymer of claim 1 , further comprising crosslinks, wherein the crosslinks comprises

wherein at least one of

is not 0.

5 . The polymer of claim 4 , wherein the crosslinks comprises one or more of

or any combination thereof.

6 . The polymer of claim 4 , wherein the polymer comprises

7 . A nanoparticle comprising the polymer of claim 1 .

8 . The nanoparticles of claim 7 , wherein the polymer is crosslinked via crosslinks, wherein the crosslinks comprises

wherein at least one of

is not 0.

9 . A method for making a polymer, the method comprising the step of polymerizing glycidol in the presence of a tin catalyst.

10 . The method of claim 9 , wherein the tin catalyst is Sn(OTf) 2 .

11 . The method of claim 9 , wherein the resultant polymer comprises repeating units selected from:

wherein R 0 is selected from H, alkyl, NH 2 , and R 1 ;
wherein R 1 comprises a crosslinking functionality;
wherein repeating units A1, A2, B1, and B2 account for at least about 50 wgt % of the polymer; and
wherein the ratio of (A1+A2):(B1+B2) is greater than 1.

12 . The method of claim 9 , wherein the resultant polymer further comprises at least one repeating unit formed from a monomer selected from:

or a combination thereof.

13 . The method of claim 9 , further comprising the step of crosslinking the polymer with crosslinks, wherein the wherein the crosslinks comprises

wherein at least one of

is not 0.

14 . The method of claim 9 , wherein the polymerization step is performed at a temperature of from −80° C. to 50° C.

16 . A method of forming a nanoparticle comprising:
(a) providing a polymer of claim 3 ; and (b) crosslinking the polymer with crosslinks, wherein the crosslinks comprises

wherein at least one of

is not 0, thereby forming a nanoparticle.

17 . A drug delivery method comprising the step of administering to a subject a composition comprising the polymer of claim 1 or the nanoparticle of claim 7 , in combination with at least one pharmaceutically active agent and/or biologically active agent.

18 . A pharmaceutical composition comprising
(a) the compound of claim 1 or a nanoparticle of claim 7 ; (b) pharmaceutically active agent and/or biologically active agent; and (c) a pharmaceutically acceptable carrier.

19 . A composition comprising
(a) a polymer comprising repeating units formed from monomers

wherein the polymer is crosslinked via crosslinks, wherein the crosslinks comprises

wherein at least one of

is not 0; and
(b) a polymer of claim 1 , wherein the polymer of claim 1 is optionally covalently bonded to the polymer.

20 . A polymer comprising a structure formed from reacting a polymer of claim 1 further comprising repeating units

with a polymer comprising at least one repeating unit formed from

Assignees

• Univ Vanderbilt

Inventors

• Harth Eva M
• Beezer Dain B
• Li Guangzhao
• Spears Benjamin R
• Stevens David M

Classifications

• A61K9/5031

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide) · CPC title

• C08G65/00

  Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule · CPC title

• C08G65/2615

  the other compounds containing carboxylic acid, ester or anhydride groups · CPC title

• C08G65/002

  from unsaturated compounds (unsaturated oxiranes C08G65/14) · CPC title

• C08G65/3326

  aromatic · CPC title