Lipid-coated particles for treating viral infections
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.
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.