Particulate coated hydrogel microparticles

Patent metadata

Field	Value
Publication number	US-11191871-B2
Application number	US-201916371806-A
Country	US
Kind code	B2
Filing date	Apr 1, 2019
Priority date	Mar 30, 2018
Publication date	Dec 7, 2021
Grant date	Dec 7, 2021

Abstract

A composition includes a plurality of particulate coated hydrogel microparticles, each of the microparticles including a hydrogel inner core and a particulate shell defined by a plurality of solid nanoparticles, the particulate shell inhibiting aggregation of the microparticles in an aqueous medium and being permeable to allow release of agents from the hydrogel inner core.

First claim

Having described the invention, we claim:

1. A method of forming a plurality of particulate coated hydrogel microparticles; the method comprising:
suspending a plurality of solid silica nanoparticles in an organic solvent;
dissolving a hydrogel forming natural polymer macromer in an aqueous solution;
adding the aqueous solution of the hydrogel forming natural polymer macromer to the organic solvent containing the solid silica nanoparticles to form a Pickering emulsion, wherein the Pickering emulsion includes a plurality of uniformly dispersed microparticles of the hydrogel forming natural polymer macromer and the solid silica nanoparticles coating outer surfaces of the hydrogel forming natural polymer macromer;
solidifying the hydrogel forming natural polymer macromer by reducing the temperature of the Pickering emulsion to the gelation temperature of the hydrogel forming natural polymer macromer and extracting water from the Pickering emulsion to form particulate silica coated hydrogel microparticles; and
isolating the particulate silica coated hydrogel microparticles from the organic solvent;
wherein the hydrogel forming natural polymer macromer includes at least one of gelatin, collagen, alginate, agarose, or a glycosaminoglycan.

2. The method of claim 1 , wherein each of the particulate silica coated hydrogel microparticles includes a hydrogel inner core and a particulate silica shell defined by a plurality of solid silica nanoparticles, the particulate silica shell inhibiting aggregation of the particulate silica coated hydrogel microparticles in an aqueous medium and being permeable to allow release of agents from the hydrogel inner core.

3. The method of claim 1 , wherein the organic solvent comprises a plant derived oil.

4. The method of claim 1 , wherein a solvent that is mixable with both phases of the Pickering emulsion is used to extract water from the Pickering emulsion.

5. The method of claim 1 , wherein the particulate silica coated hydrogel microparticles have an average diameter of about 1 μm to about 500 μm and the silica nanoparticles have an average diameter of about 1 nm to about 999 nm.

6. The method of claim 1 , wherein particulate silica coated hydrogel microparticles are isolated from the organic solvent by filtration.

7. The method of claim 1 , wherein the hydrogel forming natural polymer macromer comprise gelatin.

8. The method of claim 7 , wherein the gelatin is at least partially crosslinked.

9. The method of claim 2 , wherein the hydrogel inner core includes at least one bioactive agent, wherein the at least one bioactive agent is added to the hydrogel inner core during or after formation of the particulate silica coated hydrogel microparticles.

10. A method of forming a tissue construct, the method comprising:
suspending a plurality of solid silica nanoparticles in an organic solvent;
dissolving a hydrogel forming natural polymer macromer in an aqueous solution, wherein the hydrogel forming natural polymer macromer comprises gelatin;
adding the aqueous solution of the hydrogel forming natural polymer macromer to the organic solvent containing the solid silica nanoparticles to form a Pickering emulsion, wherein the Pickering emulsion includes a plurality of uniformly dispersed microparticles of the hydrogel forming natural polymer macromer and the solid silica nanoparticles coating outer surfaces of the hydrogel forming natural polymer macromer;
solidifying the hydrogel forming natural polymer macromer to form particulate silica coated hydrogel microparticles; and
isolating the particulate silica coated hydrogel microparticles from the organic solvent;
wherein at least one bioactive agent is loaded, incorporated, and/or encapsulated into the microparticles to provide localized, sustained, and/or controlled release of the at least one bioactive agent to cells in or about the microparticles to facilitate proliferation, growth, and/or differentiation of the cells, and
wherein the hydrogel forming polymer macromer is solidified by reducing the temperature of the Pickering emulsion to the gelation temperature of the hydrogel forming natural polymer macromer and extracting water from the Pickering emulsion to form particulate silica coated hydrogel microparticles.

11. The method of claim 10 , wherein the particulate silica coated hydrogel microparticles each include a hydrogel inner core and a particulate silica shell defined by a plurality of solid silica nanoparticles, the particulate silica shell inhibiting aggregation of the particulate silica coated hydrogel microparticles in an aqueous medium and being permeable to allow release of agents from the hydrogel inner core.

12. The method of claim 10 , wherein the organic solvent comprises a plant derived oil.

13. The method of claim 10 , wherein a solvent that is mixable with both phases of the Pickering emulsion is used to extract water.

14. The method of claim 10 , wherein the particulate silica coated hydrogel microparticles have an average diameter of about 1 μm to about 500 μm and the silica nanoparticles have an average diameter of about 1 nm to about 999 nm.

15. The method of claim 10 , wherein particulate silica coated hydrogel microparticles are isolated from the organic solvent by filtration.

16. The method of claim 10 , wherein the gelatin is at least partially crosslinked.

17. The method of claim 10 , further comprising combining the particulate silica coated hydrogel microparticles with a plurality of cells.

Assignees

• Univ Case Western Reserve

Inventors

• Alsberg Eben
• Tang Rui

Classifications

• A61K9/501

  Inorganic compounds · CPC title

• A61K9/50

  Microcapsules {having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals (A61K9/2081 takes precedence; particles with a single coating comprising drug A61K9/167)} · CPC title

• A61K9/5084

  Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs (tablets containing such a mixture A61K9/2077) · CPC title

• C08J2389/00

  Characterised by the use of proteins; Derivatives thereof · CPC title

• B82Y40/00

  Manufacture or treatment of nanostructures · CPC title