Lipid-coated particles for treating viral infections

Patent metadata

Field	Value
Publication number	US-11045554-B1
Application number	US-201916443316-A
Country	US
Kind code	B1
Filing date	Jun 17, 2019
Priority date	Jun 22, 2018
Publication date	Jun 29, 2021
Grant date	Jun 29, 2021

Abstract

The present invention relates to lipid-coated particles for treating viral infections, including viral encephalitis infections. In particular, an antiviral compound can be disposed within the lipid-coated particle, thereby providing an antiviral carrier. Methods of making and using such carriers are described herein.

First claim

The invention claimed is:

1. An antiviral carrier and compound comprising:
a porous core comprising a plurality of pores;
an antiviral compound disposed in at least one pore; and
a lipid layer disposed around the porous core,
wherein the antiviral compound has an aqueous solubility of from about 20 μg/mL to about 150 μg/mL in phosphate-buffered saline at a pH of 7.4 and/or a stability of about 80% or less of a remaining amount of the compound after incubating in plasma for about 3 hours;
wherein the compound has a structure of formula (I):

or a salt thereof;
wherein:
each R 1 , R 3 , R 4 , R 5 , and R 6 are H; and
R 2 is substituted aryl.

2. The antiviral carrier and compound of claim 1 , further comprising a pharmaceutically acceptable excipient.

3. The antiviral carrier and compound of claim 1 , wherein the antiviral compound is present in an amount of from about 10 μg/mg to 50 μg/mg (μg of the compound per mg of the carrier).

4. The antiviral carrier and compound of claim 1 , wherein the antiviral compound has a release rate of from about 3 μg/mg to about 20 μg/mg (μg of the compound per mg of the carrier) over a period of about 24 hours in vitro.

5. The antiviral carrier and compound of claim 1 , wherein the lipid layer comprises a zwitterionic lipid, a cholesterol or a derivative thereof, and a pegylated lipid.

6. The antiviral carrier and compound of claim 3 , wherein the antiviral compound has a release rate of from about 3 μg/mg to about 20 μg/mg (μg of the compound per mg of the carrier) over a period of about 24 hours in vitro;
wherein the lipid layer comprises a zwitterionic lipid, a cholesterol or a derivative thereof, and a pegylated lipid.

7. The antiviral carrier and compound of claim 5 ,
wherein the antiviral compound has a release rate of from about 3 μg/mg to about 20 μg/mg (μg of the compound per mg of the carrier) over a period of about 24 hours in vitro.

8. The antiviral carrier and compound of claim 1 , wherein the lipid layer includes about 10 to about 50 mol. % DOTAP, about 40 to 50 mol. % cholesterol, about 0 to 40 mol. % DOPE, and about 1 to 5 mol. % of a PEGylated lipid.

9. The antiviral carrier of claim 1 , wherein the antiviral compound is hydrophobic or lipophilic.

10. The antiviral carrier and compound of claim 1 , wherein the antiviral compound has an aqueous solubility of from about 20 μg/mL to about 150 μg/mL in phosphate-buffered saline at a pH of 7.4.

11. The antiviral carrier and compound of claim 1 , wherein the antiviral compound has a stability of about 80% or less of a remaining amount of the compound after incubating in plasma for about 3 hours.

12. The antiviral carrier and compound of claim 1 , wherein the antiviral compound has an EC 50 value of from about 0.01 μM to about 1 μM as determined in a cellular assay.

13. The antiviral carrier and compound of claim 12 , wherein the antiviral compound has an EC 90 value of from about 100 nM to about 300 nM as determined in a cellular assay.

14. The antiviral carrier and compound of claim 1 , wherein the antiviral compound is hydrophobic.

15. The antiviral carrier and compound of claim 1 , wherein the antiviral compound is lipophilic.

16. The antiviral carrier and compound of claim 10 , wherein the antiviral compound has a stability of about 80% or less of a remaining amount of the compound after incubating in plasma for about 3 hours.

17. The antiviral carrier and compound of claim 1 , wherein the compound is the salt of the structure of formula (I).

18. The antiviral carrier and compound of claim 1 , wherein the compound is the structure of formula (I).

19. The antiviral carrier and compound of claim 8 , wherein the antiviral compound has an EC 50 value of from about 0.01 μM to about 1 μM as determined in a cellular assay.

20. The antiviral carrier and compound of claim 17 , wherein the lipid layer includes about 10 to about 50 mol. % DOTAP, about 40 to 50 mol. % cholesterol, about 0 to 40 mol. % DOPE, and about 1 to 5 mol. % of a PEGylated lipid.

Assignees

• Nat Tech & Eng Solutions Sandia Llc
• Stc Unm

Inventors

• Negrete Oscar
• Brinker C Jeffrey
• Rinker Torri
• Labauve Annette Estelle

Classifications

• A61K9/5123

  Organic compounds, e.g. fats, sugars · CPC title

• A61K9/1271

  Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911}) · CPC title

• A61K31/517 Primary

  ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine · CPC title

• A61K31/4965

  Non-condensed pyrazines · CPC title

• A61K47/6917

  the form being a lipoprotein vesicle, e.g. HDL or LDL proteins · CPC title