Reduced and oxidized polysaccharides and methods of use thereof

Patent metadata

Field	Value
Publication number	US-2020368359-A1
Application number	US-202016992385-A
Country	US
Kind code	A1
Filing date	Aug 13, 2020
Priority date	Oct 26, 2015
Publication date	Nov 26, 2020
Grant date	—

Abstract

The present invention is directed to reduced and highly oxidized polysaccharides, such as alginates, that are useful for encapsulating therapeutic or diagnostic agents, or lipid based nanoparticles, e.g., liposomes or virosomes, encapsulating therapeutic or diagnostic agents, prior to their delivery into a subject, as well as methods for making and using them.

First claim

What is claimed is:

1 . A composition comprising a highly oxidized polysaccharide and a cross-linking agent attached to the highly oxidized polysaccharide.

2 . The composition of claim 1 , wherein said highly oxidized polysaccharide is an alginate polymer.

3 . The composition of claim 2 , wherein said highly oxidized polysaccharide comprises algoxalate having the following structure:

4 . The composition of claim 1 , wherein said highly oxidized polysaccharide is produced by a method comprising the steps of:
reacting the polysaccharide with a diol specific oxidizing agent to produce an aldehyde containing oxidized polysaccharide; and reacting said oxidized polysaccharide with a second oxidizing agent which converts aldehydes into carboxylic acids to produce said highly oxidized polysaccharide.

5 . The composition of claim 4 , wherein said diol specific oxidizing agent is sodium periodate.

6 . The composition of claim 4 , wherein said second oxidizing agent is sodium chlorite.

7 . The composition of claim 1 , wherein said cross-linking agent is a click reagent.

8 . The composition of claim 7 , wherein said click reagent is selected from the group consisting of azide, dibenzocyclooctyne (DBCO), transcyclooctene, tetrazine and norbornene and variants thereof.

9 . A hydrogel comprising the composition of claim 1 .

10 . The hydrogel of claim 9 , further comprising a therapeutic agent.

11 . The hydrogel of claim 10 , wherein said therapeutic agent is selected from the group consisting of a cell, a small molecule and a biologic.

12 . A hydrogel comprising a plurality of highly oxidized polysaccharides cross-linked to each other, wherein said hydrogel comprises a mesh size of 10 nm or less.

13 . The hydrogel of claim 12 , wherein said highly oxidized polysaccharides are highly oxidized alginate polymers.

14 . The hydrogel of claim 13 , wherein said highly oxidized alginate polymers are produced by a method comprising the steps of:
reacting an alginate with a diol specific oxidizing agent to produce an aldehyde containing oxidized alginate; and reacting said aldehyde containing oxidized alginate with a second oxidizing agent which converts aldehydes into carboxylic acids, thereby producing said highly oxidized alginate polymers.

15 . The hydrogel of claim 14 , wherein said diol specific oxidizing agent is sodium periodate.

16 . The hydrogel of claim 14 , wherein said second oxidizing agent is sodium chlorite.

17 . The hydrogel of claim 13 , wherein said highly oxidized alginate polymers are about 0.1% 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 99% oxidized.

18 . The hydrogel of claim 12 , further comprising a therapeutic or diagnostic agent.

19 . The hydrogel of claim 18 , wherein said therapeutic agent is selected from the group consisting of a cell, a small molecule and a biologic.

20 . The hydrogel of claim 12 , wherein said polysaccharides comprise a cross-linking agent attached to the polysaccharides.

21 . The hydrogel of claim 20 , wherein said cross-linking agent is a click reagent.

22 . The hydrogel of claim 21 , wherein said click reagent is selected from the group consisting of azide, dibenzocyclooctyne, transcyclooctene, tetrazine and norbornene and variants thereof.

23 . An implantable or injectable device comprising the hydrogel of claim 12 .

24 . A drug delivery composition comprising
a lipid based nanoparticle encapsulating a therapeutic or diagnostic agent; and the hydrogel of claim 12 encapsulating said lipid based nanoparticle.

25 . A method for treating a subject in need thereof, the method comprising administering to said subject an effective amount of the hydrogel of claim 12 , thereby treating said subject.

26 . A method of treating chronic ischemia or enhancing engraftment of a transplanted tissue in a subject in need thereof, the method comprising administering to said subject an effective amount of the hydrogel of claim 12 , thereby treating said chronic ischemia or enhancing engraftment of said transplanted tissue in said subject.

Assignees

• Harvard College

Inventors

• Mooney David J
• Stafford Alexander
• Desai Rajiv
• Martinick Kathleen

Classifications

• C08J2305/04

  Alginic acid; Derivatives thereof · CPC title

• C08B37/0084 Primary

  Guluromannuronans, e.g. alginic acid, i.e. D-mannuronic acid and D-guluronic acid units linked with alternating alpha- and beta-1,4-glycosidic bonds; Derivatives thereof, e.g. alginates · CPC title

• A61P27/16

  Otologicals · CPC title

• A61K9/5161

  Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin · CPC title

• A61K9/1271

  Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911}) · CPC title