Granted Patent B2

US 12,508,233 · App. 17/290,618 · Granted Dec 30, 2025

Inventors: John T. Wilson (Nashville, TN); Daniel Shae (Nashville, TN); Dinh Chuong Nguyen (Ho Chi Minh, VN)

Assignee: Vanderbilt University

A61K9/5026C08F290/062C08F2438/03

Abstract

Claims (25)

1 . A graft copolymer, comprising:

a polymer backbone of the following formula:

wherein:

Z is phenyl;

R is selected from the group consisting of alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, S, SR 1 , N, NR 1 , N(R 1 ) 2 , and combinations thereof; and R 1 is selected from the group consisting of alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, and combinations thereof; and

three segments randomly grafted to the polymer backbone, the segments being selected from a hydrophilic segment, a pH-responsive segment, and an endosomal disruption segment.

2 . The graft copolymer of claim 1 , wherein the polymer backbone and three segments form a structure according to Formula II:

wherein each of R 1 , R 2 , and R 3 independently represent one of the hydrophilic segments, the pH-responsive segments, and the endosomal disruption segments, provided that each of R 1 -R 3 are different; and

n is between 1 and 300.

3 . The graft copolymer of claim 1 , wherein R is 4-cyano-4-yl-pentanoic acid.

4 . The graft copolymer of claim 2 , wherein, when n is greater than 1, at least one repeating unit comprises a different combination of R 1 , R 2 , and R 3 from one or more other repeating units.

5 . The graft copolymer of claim 1 , wherein the hydrophilic segment is selected from the group consisting of methacrylates of polyethers, polyesters, polycarbonates, polyvinyls, polyamino acids, polysulfobetaines, carboxybetaines, and combinations thereof.

6 . The graft copolymer of claim 5 , wherein the hydrophilic segment is poly(ethylene glycol) methyl ether methacrylate (PEGMA).

7 . The graft copolymer of claim 1 , wherein the hydrophilic segment is linked to the backbone through a cleavable bond.

8 . The graft copolymer of claim 1 , wherein the pH-responsive segment is an amine containing monomer.

9 . The graft copolymer of claim 8 , wherein the amine containing monomer is selected from the group consisting of protonatable amine containing monomers, tertiary amine containing monomers, and combinations thereof.

10 . The graft copolymer of claim 8 , wherein the amine containing monomer comprises a pKa of between about 3 and about 9.

11 . The graft copolymer of claim 1 , wherein the pH-responsive segment is selected from the group consisting of (2-diethylamino)ethyl methacrylate (DEAEMA), 2-(dimethylamino)ethyl methacrylate, 2-(diisopropylamino)ethyl methacrylate, 2-N-morpholinoethyl methacrylate, 2-amino methacrylate hydrochloride, and combinations thereof.

12 . The graft copolymer of claim 1 , wherein the endosomal disruption segment is a hydrophobic monomer.

13 . The graft copolymer of claim 12 , wherein the hydrophobic monomer is selected from the group consisting of acrylates, alkyl methacrylates, methacrylates with fluorinated or aromatic pendant groups, related monomers, and combinations thereof.

14 . The graft copolymer of claim 12 , wherein the endosomal disruption segment is butyl methacrylate.

15 . The graft copolymer of claim 2 , wherein the graft copolymer has the structure:

16 . The graft copolymer of claim 1 , further comprising a hydrophilic weight fraction selected from the group consisting of up to about 25% and between about 26% and about 30%.

17 . A method of delivering an active agent to a subject in need thereof, the method comprising encapsulating the active agent with the graft copolymer of claim 1 and administering the encapsulated active agent to the subject.

18 . The graft copolymer of claim 1 , further comprising an active agent encapsulated therein.

Assignments (1)

Continuity (2)

References Cited (14)