Acid-degradable and bioerodible modified polyhydroxylated materials

Patent metadata

Field	Value
Publication number	US-10995156-B2
Application number	US-201715474827-A
Country	US
Kind code	B2
Filing date	Mar 30, 2017
Priority date	Mar 24, 2006
Publication date	May 4, 2021
Grant date	May 4, 2021

Abstract

Compositions and methods of making a modified polyhydroxylated polymer comprising a polyhydroxylated polymer having reversibly modified hydroxyl groups, whereby the hydroxyl groups are modified by an acid-catalyzed reaction between a polydroxylated polymer and a reagent such as acetals, aldehydes, vinyl ethers and ketones such that the modified polyhydroxylated polymers become insoluble in water but freely soluble in common organic solvents allowing for the facile preparation of acid-sensitive materials. Materials made from these polymers can be made to degrade in a pH-dependent manner. Both hydrophobic and hydrophilic cargoes were successfully loaded into particles made from the present polymers using single and double emulsion techniques, respectively. Due to its ease of preparation, processability, pH-sensitivity, and biocompatibility, of the present modified polyhydroxylated polymers should find use in numerous drug delivery applications.

First claim

What is claimed is:

1. An acid-degradable modified polyhydroxylated polymer comprising pendant hydroxyl groups, wherein at least 20% of the pendant hydroxyl groups are each directly linked to an acid degradable functional group, wherein the modified polyhydroxylated polymer is insoluble in water.

2. The acid-degradable modified polyhydroxylated polymer of claim 1 , wherein each functional group is selected from the group consisting of acetals, aromatic acetals, and ketals.

3. The acid-degradable modified polyhydroxylated polymer of claim 1 , wherein the polyhydroxylated polymer is selected from the group consisting of multiply-hydroxylated polymers, polysaccharides, carbohydrates, polyols, polyvinyl alcohol, poly amino acids, polyserine, and 2-(hydroxyethyl)methacrylate.

4. The acid-degradable modified polyhydroxylated polymer of claim 3 , wherein the polyhydroxylated polymer is a polysaccharide.

5. The acid-degradable modified polyhydroxylated polymer of claim 4 , wherein the polysaccharide is selected from the group consisting of dextran, mannan, pullulan, maltodextrin, starches, cellulose and cellulose derivatives, xanthan gum, locust bean gum, and pectin.

6. The acid-degradable modified polyhydroxylated polymer of claim 5 , wherein the polysaccharide is dextran or mannan.

7. The acid-degradable modified polyhydroxylated polymer of claim 1 , wherein each acid degradable functional group is an acetal.

8. The acid-degradable modified polyhydroxylated polymer of claim 7 , wherein the polyhydroxylated polymer is acetal-derivatized dextran, acetal-derivatized mannan or acetal-derivatized polyvinyl alcohol.

9. The acid-degradable modified polyhydroxylated polymer of claim 1 , wherein at least 20% to 85% of the hydroxyl groups in the polyhydroxylated polymer are modified.

10. The acid-degradable modified polyhydroxylated polymer of claim 1 , wherein the polymer is in the form of a particle.

11. The acid-degradable modified polyhydroxylated polymer of claim 1 , further comprising a bioactive material conjugated or entrapped therein.

12. The acid-degradable modified polyhydroxylated polymer of claim 11 , wherein said polymer is in the form of particles, sutures, bulk materials, tissue engineering scaffolds, or implants.

13. The acid-degradable modified polyhydroxylated polymer of claim 11 , wherein the bioactive material is selected from the group consisting of polynucleotides, polypeptides, proteins, peptides, antibodies, vaccines, antigens, small molecule drugs, ribonucleotides, amino acids, oligopeptides, peptoids, proteins, plasmid DNA, growth factors and hormones, interleukins, immunostimulatory agents, neurotransmitters, neurostimulatory agents, adrenergic agents, neuromodulatory agents, enzymes, proteases, anticancer agents, antitumor agents, imaging agents, diagnostic agents, antiviral agents, antibacterial agents and therapeutic agents.

14. The acid-degradable modified polyhydroxylated polymer of claim 13 , wherein the bioactive material is a polynucleotide.

15. The acid-degradable modified polyhydroxylated polymer of claim 13 , wherein the bioactive material is a therapeutic agent.

16. The acid-degradable modified polyhydroxylated polymer of claim 13 , wherein the bioactive material is a vaccine.

17. A vaccine composition comprising an acid-degradable modified polyhydroxylated polymer of claim 1 , and a bioactive material conjugate or entrapped therein.

18. The composition of claim 17 , wherein the bioactive material is selected from the group consisting of polynucleotides, polypeptides, proteins, peptides, antibodies, vaccines, antigens, small molecule drugs, ribonucleotides, amino acids, oligopeptides, peptoids, proteins, plasmid DNA, growth factors and hormones, interleukins, immunostimulatory agents, neurotransmitters, neurostimulatory agents, adrenergic agents, neuromodulatory agents, enzymes, proteases, anticancer agents, antitumor agents, imaging agents, diagnostic agents, antiviral agents, antibacterial agents and therapeutic agents.

19. The composition of claim 17 , wherein the bioactive material is a polynucleotide.

20. The composition of claim 17 , wherein the bioactive material is a therapeutic agent.

21. A drug-delivery particle comprising an acid-degradable modified polyhydroxylated polymer of claim 1 .

22. A method of delivering a bioactive material to a cellular interior, comprising:
contacting the cell with acid-degradable particles comprising a bioactive material bound within or conjugated to an acid-degradable modified polyhydroxylated polymer of claim 1 , whereby hydrolysis within an acidic cellular compartment cleaves the acid-degradable functional groups in said modified polyhydroxylated polymer and releases said bioactive material.

Assignees

• Univ California

Inventors

• Frechet Jean M J
• Bachelder Eric M
• Beaudette Tristan T
• Broaders Kyle E

Classifications

• A61K39/00

  Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53) · CPC title

• A61K39/0011

  Cancer antigens · CPC title

• A61K47/6939

  the polymer being a polysaccharide, e.g. starch, chitosan, chitin, cellulose or pectin · CPC title

• A61K47/50

  the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates · CPC title

• C08F216/38

  by an acetal or ketal radical · CPC title