Biodegradable polymers, complexes thereof for gene therapeutics and drug delivery, and methods related thereto

Patent metadata

Field	Value
Publication number	US-2020079901-A1
Application number	US-201916687724-A
Country	US
Kind code	A1
Filing date	Nov 19, 2019
Priority date	Dec 23, 2009
Publication date	Mar 12, 2020
Grant date	—

Abstract

A biodegradable cationic polymer is disclosed, comprising first repeat units derived from a first cyclic carbonyl monomer by ring-opening polymerization, wherein more than 0% of the first repeat units comprise a side chain moiety comprising a quaternary amine group; a subunit derived from a monomeric diol initiator for the ring-opening polymerization; and an optional endcap group. The biodegradable cationic polymers have low cytotoxicity and form complexes with biologically active materials useful in gene therapeutics and drug delivery.

First claim

What is claimed is:

1 . A polymer complex, comprising:
a negatively charged biologically active material selected from the group consisting of genes, nucleotides, proteins, peptides, drugs, and combinations thereof; and a biodegradable cationic polymer comprising
i) a first repeat unit selected from the group consisting of

 and
ii) an optional second repeat unit;

wherein
the biologically active material and the cationic polymer are bound together by non-covalent interactions, and
the polymer complex is capable of entering a cell by endocytosis and releasing the biologically active material within the cell.

2 . The polymer complex of claim 1 , wherein the first repeat unit is

3 . The polymer complex of claim 1 , wherein the first repeat unit is

4 . The polymer complex of claim 1 , wherein the first repeat unit is

5 . The polymer complex of claim 1 , wherein the cationic polymer is a polycarbonate homopolymer of the first repeat unit.

6 . The polymer complex of claim 1 , wherein the cationic polymer is a polycarbonate random copolymer of the first repeat unit and the second repeat unit, wherein the second repeat unit is selected from the group consisting of

7 . The polymer complex of claim 6 , wherein the second repeat unit is

8 . The polymer complex of claim 1 , wherein cationic polymer is a diblock copolymer comprising i) a hydrophobic core block and ii) a hydrophilic outer block linked to the hydrophobic core block, the hydrophilic outer block comprising the first repeat unit.

9 . The polymer complex of claim 8 , wherein the hydrophobic core block is a polycarbonate.

10 . The polymer complex of claim 9 , wherein the hydrophobic core block is a poly(trimethylene carbonate).

11 . The polymer complex of claim 8 , wherein the hydrophobic core block is a polyester.

12 . The polymer complex of claim 11 , wherein the hydrophobic core block is poly(L-lactide).

13 . The polymer complex of claim 11 , wherein the hydrophobic core block is poly(D-lactide).

14 . The polymer complex of claim 1 , wherein the cationic polymer self-assembles in water to form nanoparticles having an average particle size of 10 nm to 500 nm at a pH of from 5.0 to 8.0.

15 . The polymer complex of claim 14 , wherein in water the nanoparticles of the cationic polymer have a positively charged surface and a hydrophobic core.

16 . The polymer complex of claim 1 , wherein the polymer complex in water has an average particle size of 50 nm to 500 nm at a pH of from 5.0 to 8.0.

17 . The polymer complex of claim 1 , wherein the biologically active material is a gene.

18 . The polymer complex of claim 1 , wherein the biologically active material is a drug.

19 . The polymer complex of claim 1 , wherein the cationic polymer is biodegradable in accordance with ASTM D6400.

20 . A method of treating a cell, comprising:
contacting the cell with nanoparticles of the polymer complex of claim 1 in water, wherein the polymer complex enters the cell, the polymer complex releases the biologically active material within the cell, and the released biologically active material alters a chemical structure and/or activity of the cell.

21 . The method of claim 20 , wherein the nanoparticles have an average particle size of 50 nm to 500 nm at a pH of from 5.0 to 8.0.

22 . The method of claim 20 , wherein the cell is a eukaryotic cell.

23 . The method of claim 22 , wherein the biologically active material is a gene, the polymer complex releases the gene within the cell, and the gene is incorporated into deoxyribonucleic acid (DNA) of the cell.

24 . The method of claim 23 , wherein the cell expresses the gene.

25 . The method of claim 20 , wherein the biologically active material is a drug.

Assignees

• IBM
• Agency Science Tech & Res

Inventors

• Fukushima Kazuki
• Hedrick James L
• Yang Yiyan

Classifications

• C08G64/18

  Block or graft polymers · CPC title

• C08G64/0241

  containing nitrogen · CPC title

• C08G63/912

  derived from hydroxycarboxylic acids · CPC title

• C08G2261/126

  block · CPC title

• Y02P20/582

  Recycling of unreacted starting or intermediate materials · CPC title