Mineral coated microparticles for co-delivery of anti-inflammatory molecules with nucleic acids to improve gene delivery outcomes

Patent metadata

Field	Value
Publication number	US-11065208-B2
Application number	US-201816626973-A
Country	US
Kind code	B2
Filing date	Jul 5, 2018
Priority date	Jul 5, 2017
Publication date	Jul 20, 2021
Grant date	Jul 20, 2021

Abstract

Disclosed are compositions and methods for the co-delivery of ribonucleic acids and interferon binding proteins. Compositions include mineral coated microparticles having a mineral layer, a ribonucleic acid, and an interferon binding protein. Ribonucleic acids and interferon binding proteins can be adsorbed to the mineral layer, can be incorporated into the mineral layer, and combinations thereof. Also disclosed are methods for co-delivery of ribonucleic acids and interferon binding proteins and methods for treating inflammatory diseases using mineral coated microparticles having a mineral layer to provide co-delivery of ribonucleic acids and interferon binding proteins.

First claim

What is claimed is:

1. A composition comprising:
a mineral coated microparticle comprising:
at least one mineral layer;
a ribonucleic acid and at least one of an interferon binding protein and an interferon inhibitor.

2. The composition of claim 1 , wherein at least one of the ribonucleic acid; an interferon binding protein; an interferon inhibitor; and combinations thereof is adsorbed to the mineral layer or incorporated within the mineral layer.

3. The composition of claim 1 , wherein the ribonucleic acid is a messenger ribonucleic acid (mRNA).

4. The composition of claim 1 , wherein the interferon binding protein is selected from the group consisting of B18R, E3L interferon resistance protein, K3L, Non-Structural Protein 1, New World Arenaviruses Z proteins, V protein, 3C, leader proteinase, E6, N pro , NS5A, and combinations thereof.

5. The composition of claim 1 , wherein the at least one mineral layer comprises calcium, phosphate, carbonate, and combinations thereof.

6. The composition of claim 1 , wherein the at least one mineral layer further comprises a halogen selected from the group consisting of fluorine, chlorine, bromine, iodine, astatine, and combinations thereof.

7. The composition of claim 1 , further comprises a core selected from the group consisting of polymers, ceramics, metals, glass, and combinations thereof.

8. The composition of claim 1 , wherein the at least one mineral layer comprises a plurality of mineral layers, and the plurality of mineral layers comprise the same mineral composition or different mineral compositions.

9. The composition of claim 1 , wherein the interferon inhibitor is a small molecule interferon inhibitor selected from the group consisting of BX795, MRT68844, MRT67307, TPCA-1, Cyt387, AZD1480, Ruxolitinib, Tofacitinib, and combinations thereof.

10. The composition of claim 1 , wherein the at least one mineral layer comprises a morphology selected from the group consisting of spherulite-like, plate-like, net-like, needle-like, and combinations thereof.

11. A method for delivery of a ribonucleic acid and at least one of an interferon binding protein and an interferon inhibitor, the method comprising:
administering a composition comprising a mineral coated microparticle comprising at least one mineral layer; a ribonucleic acid and at least one of an interferon binding protein and an interferon inhibitor.

12. The method of claim 11 , wherein the ribonucleic acid is a messenger ribonucleic acid (mRNA).

13. The method of claim 11 , wherein the interferon binding protein is selected from the group consisting of B18R, E3L interferon resistance protein, K3L, Non-Structural Protein 1, New World Arenaviruses Z proteins, V protein, 3C, leader proteinase, E6, N pro , NS5A, and combinations thereof.

14. The method of claim 11 , wherein the at least one mineral layer comprises calcium, phosphate, carbonate, and combinations thereof.

15. The composition of claim 11 , wherein the at least one mineral layer further comprises a halogen selected from the group consisting of fluorine, chlorine, bromine, iodine, astatine and combinations thereof.

16. The method of claim 11 , wherein the at least one mineral layer comprises a plurality of mineral layers, and the plurality of mineral layers comprise the same mineral composition or different mineral compositions.

17. The method of claim 11 , wherein the interferon inhibitor is a small molecule interferon inhibitor selected from the group consisting of BX795, MRT68844, MRT67307, TPCA-1, Cyt387, AZD1480, Ruxolitinib, Tofacitinib and combinations thereof.

18. The method of claim 11 , wherein the at least one mineral layer comprises a morphology selected from the group consisting of spherulite-like, plate-like, net-like, needle-like, and combinations thereof.

19. A method for treating an inflammatory disease in a subject in need thereof, the method comprising:
administering a composition comprising a mineral coated microparticle to the subject, the mineral coated microparticle comprising at least one mineral layer; a ribonucleic acid and at least one of an interferon binding protein and an interferon inhibitor.

20. The method of claim 19 , wherein the interferon binding protein is selected from the group consisting of B18R, E3L interferon resistance protein, K3L, Non-Structural Protein 1, New World Arenaviruses Z proteins, V protein, 3C, leader proteinase, E6, N pro , NS5A, and combinations thereof.

Assignees

• Wisconsin Alumni Res Found

Inventors

• Murphy William L
• Khalil Andrew Salim
• Yu Xiaohua

Classifications

• A61K9/10

  Dispersions; Emulsions · CPC title

• A61K9/501 Primary

  Inorganic compounds · CPC title

• A61K9/19

  lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)} · CPC title

• C07K14/715 Primary

  for cytokines; for lymphokines; for interferons · CPC title

• A61K48/0033

  the non-active part being non-polymeric · CPC title