# US 2021/0330809 A1 · Lipid-coated particles for treating viral infections

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- Number: US 2021/0330809 A1
- Document ID: US20210330809A1
- Status: Published application
- Kind: A1
- Application number: 17/306,452
- Filed: 2021-05-03
- Published: 2021-10-28
- Earliest claimed: 2018-06-22
- Assignees: National Technology & Engineering Solutions of Sandia, LLC; UNM Rainforest Innovations
- Applicants: National Technology & Engineering Solutions of Sandia, LLC; UNM Rainforest Innovations
- Inventors: Oscar Negrete; C. Jeffrey Brinker; Torri Rinker; Annette Estelle LaBauve
- Web page: https://patentgrep.com/patent/US20210330809A1

## CPC

- A61K 47/6915: {the form being a liposome with polymerisable or polymerized bilayer-forming substances, e.g. polymersomes}
- A61K 9/1271: Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911})
- A61K 9/5123: {Organic compounds, e.g. fats, sugars}
- A61K 31/4965: Non-condensed pyrazines
- A61K 31/517: ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
- A61K 47/543: {Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine}
- A61K 47/6913: {the liposome being modified on its surface by an antibody}
- A61K 47/6917: {the form being a lipoprotein vesicle, e.g. HDL or LDL proteins}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## 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.

## Claims

### Claim 1

A method of reducing brain viral load within a subject, the method comprising:
administering an effective amount of a lipid-coated particle to the subject, wherein the lipid-coated particle comprises a porous core and an antiviral compound disposed within at least one pore of the porous core.

### Claim 2 (depends on 1)

The method 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 and/or a stability of about 80% or less of a remaining amount of the compound after incubating in plasma for about 3 hours.

### Claim 3 (depends on 1)

The method of claim 1, wherein the administering is performed via intravenous, intramuscular, intraperitoneal, retro-orbital, or subcutaneous injection.

### Claim 4 (depends on 1)

The method of claim 1, wherein a lipid layer of the lipid-coated particle 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.

### Claim 5 (depends on 1)

The method of claim 1, wherein the lipid-coated particle has a (diameter) ranging from about 0.5 to about 30 nm, about 1 nm to about 30 nm.

### Claim 6 (depends on 1)

The method of claim 1, wherein the lipid-coated particle is monodisperse and colloidally stable.

### Claim 7 (depends on 1)

The method of claim 1, wherein the brain viral load includes an encephalitic alphavirus infection.

### Claim 8 (depends on 7)

The method of claim 7, wherein the encephalitic alphavirus is Venezuelan Equine Encephalitis Virus.

### Claim 9 (depends on 1)

The method of claim 1, wherein the antiviral compound has a structure of formula (I) or (II) or (III):
or a salt thereof, wherein:
each R1 is, independently, H or optionally substituted alkyl;
each R2 is, independently, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted alkaryl, or optionally substituted alkheterocyclyl;
each R4, R5, R7, and R8 is, independently, H, optionally substituted alkyl, halo, nitro, amino, azido, cyano, hydroxyl, optionally substituted hydroxyalkyl, optionally substituted haloalkyl, optionally substituted perfluoroalkyl, or optionally substituted cycloalkyl, or in which R4 and R5, taken together, or R7 and R8, taken together, form an optionally substituted spirocyclyl; and
each R3 and R6 is, independently, H, optionally substituted alkyl, halo, nitro, nitroso, amino, azido, carboxyl, cyano, hydroxyl, optionally substituted hydroxyalkyl, optionally substituted haloalkyl, optionally substituted perfluoroalkyl, or optionally substituted cycloalkyl.

### Claim 10 (depends on 1)

The method 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 lipid-coated particle).

### Claim 11 (depends on 1)

The method of claim 1, wherein the antiviral compound is released at a rate of from about 3 μg/mg to about 20 μg/mg (μg of the compound per mg of the lipid-coated particle) over a period of about 24 hours in vitro.

### Claim 12

A method of treating cancer within a subject, the method comprising:
administering an effective amount of a lipid-coated particle to the subject, wherein the lipid-coated particle comprises a porous core and an anticancer compound disposed within at least one pore of the porous core.

### Claim 13

A method of increasing a stability and/or a solubility of an antiviral compound within an aqueous solution, the method comprising:
incubating the antiviral compound with a core comprising a plurality of pores, thereby providing a loaded core; and
coating the loaded core with a lipid layer, thereby provided a lipid-coated particle,
wherein the stability and/or the solubility of the lipid-coated particle within the aqueous solution is greater than the stability and/or the solubility of the antiviral compound within the aqueous solution.

### Claim 14 (depends on 13)

The method of claim 13, 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 antiviral compound after incubating in plasma for about 3 hours.

### Claim 15 (depends on 13)

The method of claim 13, wherein the compound has a structure of formula (I) or (II) or (III):
or a salt thereof, wherein:
each R1 is, independently, H or optionally substituted alkyl;
each R2 is, independently, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted alkaryl, or optionally substituted alkheterocyclyl;
each R4, R5, R7, and R8 is, independently, H, optionally substituted alkyl, halo, nitro, amino, azido, cyano, hydroxyl, optionally substituted hydroxyalkyl, optionally substituted haloalkyl, optionally substituted perfluoroalkyl, or optionally substituted cycloalkyl, or in which R4 and R5, taken together, or R7 and R8, taken together, form an optionally substituted spirocyclyl; and
each R3 and R6 is, independently, H, optionally substituted alkyl, halo, nitro, nitroso, amino, azido, carboxyl, cyano, hydroxyl, optionally substituted hydroxyalkyl, optionally substituted haloalkyl, optionally substituted perfluoroalkyl, or optionally substituted cycloalkyl.

### Claim 16 (depends on 13)

The method of claim 13, wherein the antiviral compound has a release rate of from about 3 μg/mg to about 20 μg/mg (μg of the antiviral compound per mg of the lipid-coated particle) over a period of about 24 hours in vitro.

### Claim 17 (depends on 13)

The method of claim 13, wherein the lipid layer comprises a zwitterionic lipid, a cholesterol or a derivative thereof, and a pegylated lipid.

### Claim 18 (depends on 13)

The method of claim 13, wherein the antiviral compound has an EC50 value of from about 0.01 μM to about 1 μM as determined in a cellular assay.

### Claim 19 (depends on 18)

The method of claim 18, wherein the antiviral compound has an EC90 value of from about 100 nM to about 300 nM as determined in a cellular assay.

### Claim 20 (depends on 13)

The method of claim 13, wherein the antiviral compound is hydrophobic or lipophilic.