Microparticles, methods for their preparation and use

• US 10,471,016 B2
• Filed: 03/08/2018
• Issued: 11/12/2019
• Est. Priority Date: 11/08/2013
• Status: Active Grant

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Mooney, David J., Weitz, David A., Utech, Stefanie, Prodanovich, Radivoje, Amstad, Esther, Ostafe, Raluca, Mao, Angelo S., Wilking, Connie Chang, Wang, Huanan
• Primary Examiner(s): Azpuru, Carlos A
• Application Number:
  US15/915,686
• Publication Number:
  US 20180214385A1
• Time in Patent Office: 614 Days
• CPC Class Codes: A61K 35/00 Medicinal preparations containing materials or reaction products thereof with undetermined constitution
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/5036 Polysaccharides, e.g. gums, alginate; Cyclodextrin
• CPC Class Codes: A61K 9/5089 Processes

Abstract

The invention relates to microparticles comprising a crosslinked gel and methods for making and using same.

Claims

1. A method of forming microparticles, comprising:

passing a plurality of microdroplets comprising a gel precursor through a curved microfluidic channel having at least one dimension measuring from about 5 μ

m to about 200 μ

m; and

crosslinking the gel precursor to form a plurality of microparticles comprising a crosslinked gel, the microparticles having a shape conforming to the shape of the curved microfluidic channel.

2. The method of claim 1, wherein the microparticles have a coefficient of variation in size distribution of from about 0.03 to about 0.05.

3. The method of claim 1, wherein the microparticles are crescent- or hook-shaped.

4. The method of claim 1, wherein crosslinking the gel precursor to form a plurality of microparticles comprises microfluidically forming the microdroplets.

5. The method of claim 1, wherein the gel precursor comprises one or more crosslinkable linear polysaccharides and one or more crosslinking agents.

6. The method of claim 5, comprising crosslinking the gel precursor with a crosslinking promoter to promote crosslinking of the one or more crosslinkable linear polysaccharides.

7. The method of claim 6, wherein the crosslinking agent does not substantially crosslink the one or more crosslinkable linear polysaccharides in an initial state, but upon contacting with the crosslinking promoter, crosslinks the one or more crosslinkable linear polysaccharides in a second state.

8. The method of claim 7, wherein the initial state comprises a sequestered state of the one or more crosslinking agents and the second state comprises an unsequestered state of the one or more crosslinking agents.

9. The method of claim 6, wherein said crosslinking promoter comprises a change in pH, a change in temperature, a change in ionic strength or combinations thereof.

10. The method of claim 9, wherein said crosslinking promoter comprises a change in the pH.

11. The method of claim 10, wherein the change in the pH is effected with an acid.

12. The method of claim 6, wherein the crosslinking agent comprises divalent cations.

13. The method of claim 12, wherein the divalent cations are sequestered.

14. The method of claim 13, wherein the sequestered divalent cations are chelated.

15. The method of claim 14, wherein the chelated divalent cations comprise Ca²⁺-EDTA.

16. The method of claim 12, wherein the divalent cations are sequestered and the crosslinking promoter causes the sequestered divalent cations to be sufficiently freed from sequestration such that crosslinking of the one or more crosslinkable linear polysaccharides is promoted.