Polymers and polymeric nanogels with hydrophilics encapsulation and release capabilities and methods thereof

Patent metadata

Field	Value
Publication number	US-10617652-B2
Application number	US-201515508955-A
Country	US
Kind code	B2
Filing date	Sep 17, 2015
Priority date	Sep 17, 2014
Publication date	Apr 14, 2020
Grant date	Apr 14, 2020

Abstract

The invention provides pH- or redox-responsive and charge-neutral polymeric nanogels that stably encapsulate a biomolecule at one pH or redox condition and then release it at a different pH or redox condition, and compositions and methods of preparation and use thereof.

First claim

The invention claimed is:

1. A crosslinked polymeric nanogel, adapted to stably encapsulate a hydrophilic biomolecule at a first pH condition and then release it at a second pH condition, wherein the crosslinked polymeric nanogel is crosslinked with an acid-labile crosslinker and comprises the structural unit:

wherein
each of R 1 , R 2 , R 3 R 4 , R 5 and R 6 is independently a hydrogen, C 1 -C 12 alkyl group, or halogen;
each of x and y is independently a positive number;
each of m and p is independently an integer from about 1 to about 10;
n is a positive number from 1 to about 200; and
X is independently chosen from O and NH.

2. The crosslinked polymeric nanogel of claim 1 , wherein each of R 1 , R 2 , R 3 , R 4 , R 5 and R 6 is a hydrogen.

3. The crosslinked polymeric nanogel of claim 1 , wherein the second pH is lower than the first pH.

4. The crosslinked polymeric nanogel of claim 3 , wherein the second pH is from about 3.5 to about 6.4 and the first pH is from about 6.5 to about 8.0.

5. A crosslinked polymeric nanogel, adapted to stably encapsulate a hydrophilic biomolecule at a first redox condition and then release it at a second redox condition, wherein the crosslinked polymeric nanogel is crosslinked with a redox-labile crosslinker and comprises the structural unit:

wherein
each of R 1 , R 2 , R 3 R 4 , R 5 and R 6 is independently a hydrogen, C 1 -C 12 alkyl group, or halogen;
R 7 is independently a hydrogen, C 1 -C 12 alkyl group, or an ethyleneglycol chain with 2 to about 200 repeat units;
each of x and y is independently a positive number;
n is a positive number from 1 to about 200; and
X is independently chosen from O or NH.

6. The crosslinked polymeric nanogel of claim 5 , wherein each of R 1 , R 2 , R 3 , R 4 , R 5 and R 6 is a hydrogen.

7. The crosslinked polymeric nanogel of claim 5 , wherein the redox-labile crosslinker comprises one or more moieties selected from acrylate, methacrylate or a disulfide moiety.

Assignees

• Univ Massachusetts

Inventors

• Thayumanavan Sankaran
• Molla Mijanur Rahaman
• Garman Scott Clayton

Classifications

• C12N15/111

  General methods applicable to biologically active non-coding nucleic acids · CPC title

• C12N2310/11

  Antisense · CPC title

• A61K9/1075

  Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers (A61K9/0026 takes precedence) · CPC title

• A61K31/713

  Double-stranded nucleic acids or oligonucleotides · CPC title

• C12N2310/16

  Aptamers · CPC title