Amphiphilic nucleotide cochleate compositions and methods of using the same
View Patent ↗The present invention is directed to siRNA-cochleate compositions that include a siRNA that is associated with a cochleate and a positively charged amphiphile. The present invention also includes methods for making and using the compositions provided herein.
1. A siRNA-cochleate composition comprising:
a cochleate; and
a short interfering ribonucleic acid (siRNA) associated with the cochleate;
wherein the siRNA is associated with a positively charged amphiphile, wherein the positively charged amphiphile is a compound of formula (I):
wherein:
R is selected from H, a C2-C26 acyl group and a C4-C26 aliphatic group;
R 1 is selected from
R 2 and R 3 are each independently a C4-C26 aliphatic group;
optionally one or more of R, R 2 and R 3 is:
R 4 and R 5 are each independently a C3-C20 aliphatic group;
n is an integer from 1 to 3; and
X − is an anion of a pharmaceutically acceptable compound.
2. The composition of claim 1 , wherein R is selected from nonanoyl, dodecanoyl, myristoyl, palmitoyl, steroyl, oleoyl, oleyl, nonyl, undecyl, tetradecyl, and hexadecyl.
3. The composition of claim 1 , wherein R 1 is
4. The composition of claim 3 , wherein R 3 is selected from oleyl, nonyl, undecyl, tetradecyl, and hexadecyl.
5. A siRNA-cochleate composition comprising:
a cochleate; and
a short interfering ribonucleic acid (siRNA) associated with the cochleate;
wherein the siRNA is associated with a positively charged amphiphile, wherein the positively charged amphiphile is a compound of formula (II):
wherein:
R is selected from H, a C2-C26 acyl group and a C4-C26 aliphatic group;
R 2 is a C4-C26 aliphatic group;
optionally one or both of R and R 2 is:
R 4 and R 5 are each independently a C3-C20 aliphatic group;
n is an integer from 1 to 3; and
X − is an anion of a pharmaceutically acceptable compound.
6. The composition of claim 5 , wherein R is selected from nonanoyl, dodecanoyl, myristoyl, palmitoyl, steroyl, oleoyl, oleyl, nonyl, undecyl, tetradecyl, and hexadecyl.
7. The composition of claim 5 , wherein R 2 is selected from oleyl, nonyl, undecyl, tetradecyl and hexadecyl.
8. A siRNA-cochleate composition comprising:
a cochleate; and
a short interfering ribonucleic acid (siRNA) associated with the cochleate;
wherein the siRNA is associated with a positively charged amphiphile, wherein the positively charged amphiphile is a compound of formula (III):
wherein:
R is selected from a C2-C26 acyl group, a C4-C26 aliphatic group and H;
R 4 and R 5 are each independently a C3-C20 aliphatic group;
n is an integer from 1 to 3; and
X − is an anion of a pharmaceutically acceptable compound.
9. The composition of claim 8 , wherein R is selected from nonanoyl, dodecanoyl, myristoyl, palmitoyl, steroyl, oleoyl, oleyl, nonyl, undecyl, tetradecyl, hexadecyl, acetyl, propionyl, butyryl, valeryl, and isovaleryl.
10. The composition of claim 8 , wherein —(C═O)—R 4 and —(C═O)—R 5 are each independently selected from hexanoyl, undecanoyl, myristoyl, palmitoyl and oleoyl.