PEGylated liposomes and methods of use
Provided herein are PEGylated liposomes, and methods of making and using thereof. The PEGylated liposomes comprise at least a cholesterol, a non-PEGylated neutral lipid, and a PEGylated lipid, wherein the average molecular weight of the PEG component in the PEGylated lipid is about 5000 Daltons or less. The PEGylated liposomes are stable and capable of delivery of an agent for the generation of an immune response, for example an agent for vaccine, therapeutic, or diagnostic uses. Compositions and methods related to making the PEGylated liposomes and using the PEGylated liposomes for stimulating an immune response are also provided.
1. A liposome comprising:
an antigen;
a cholesterol;
a non-PEGylated neutral lipid;
a PEGylated lipid, wherein an average molecular weight of the PEG in the PEGylated lipid is about 2000 Daltons, wherein a lipid molar ratio of the non-PEGylated neutral lipid:cholesterol:PEGylated lipid is about 9.8:5.7:0.8 or about 18:5.5:3; and
agonists comprising GLA and 3M-052, wherein there is at least about twice as much GLA as 3M-052 by weight and wherein the GLA comprises a synthetic GLA of formula:
or a pharmaceutically acceptable salt thereof; or
a synthetic GLA of formula (VI):
or a pharmaceutically acceptable salt thereof, wherein R 1 , R 3 , R 5 and R 6 are C 11 -C 20 alkyl; and R 2 and R 4 are C 12 -C 20 alkyl.
2. The liposome of claim 1 , wherein the lipid component of the PEGylated lipid is DSPE, DPPC, DOPC, DLPC, DMPC, DSPC, POPC, DPPE, or DMPE.
3. The liposome of claim 1 , wherein the lipid component of the PEGylated lipid comprises a C 14 alkyl chain, a C 16 alkyl chain, or a C 18 alkyl chain.
4. The liposome of claim 1 , wherein the non-PEGylated neutral lipid is DPPC, DOPC, DLPC, DMPC, DSPC, POPC, DPPE, or DMPE.
5. The liposome of claim 1 , wherein the non-PEGylated neutral lipid comprises a C 14 alkyl chain, a C 16 alkyl chain, or a C 18 alkyl chain.
6. The liposome of claim 1 , wherein a polydispersity index of the liposome is maintained at about 0.3 or less.
7. The liposome of claim 1 , wherein a size of the liposome is less than or about 450 nm.
8. The liposome of claim 1 , wherein the antigen comprises H5N1.
9. The liposome of claim 1 , wherein the antigen comprises LecA.
10. The liposome of claim 1 , further comprising an antioxidant.
11. The liposome of claim 10 , wherein the antioxidant comprises ascorbic acid, sodium bisulfate, or α-tocopherol.
12. A liposome comprising:
an antigen;
a cholesterol;
non-PEGylated neutral lipid comprising DMPC, DPPC, DSPC, or DOPC;
a PEGylated lipid comprising DMPE, DPPE, or DSPE that is PEGylated with a PEG having an average molecular weight of about 2000 Daltons, wherein a lipid molar ratio of the non-PEGylated neutral lipid:cholesterol:PEGylated lipid is about 9.8:5.7:0.8; and
agonists comprising GLA and 3M-052, wherein there is at least about twice as much GLA as 3M-052 by weight and wherein the GLA comprises a synthetic GLA of formula:
or a pharmaceutically acceptable salt thereof; or
a synthetic GLA of formula (VI):
or a pharmaceutically acceptable salt thereof, wherein R 1 , R 3 , R 5 and R 6 are C 11 -C 20 alkyl; and R 2 and R 4 are C 12 -C 20 alkyl.
13. The liposome of claim 1 , wherein the cholesterol is present at about 1-50 mol %, the non-PEGylated neutral lipid is present at about 45-98 mol %, and the PEGylated lipid is present at about 1-25 mol %.
14. The liposome of claim 13 , wherein the cholesterol is present at about 50 mol %, the non-PEGylated neutral lipid is present at about 45 mol %, and the PEGylated lipid is present at about 5 mol %.
15. The liposome of claim 1 , wherein there is at about 2.5 times as much GLA as 3M-052 by weight.
16. The liposome of claim 12 , wherein the cholesterol is present at about 1-50 mol %, the non-PEGylated neutral lipid is present at about 45-98 mol %, and the PEGylated lipid is present at about 1-25 mol %.
17. The liposome of claim 16 , wherein the cholesterol is present at about 50 mol %, the non-PEGylated neutral lipid is present at about 45 mol %, and the PEGylated lipid is present at about 5 mol %.
18. The liposome of claim 12 , further comprising an antioxidant.
19. The liposome of claim 12 , wherein there is at about 2.5 times as much GLA as 3M-052 by weight.
20. The liposome of claim 1 , wherein R 1 , R 3 , R 5 , and R 6 are C 11 alkyl; and R 2 and R 4 are C 13 alkyl.
21. The liposome of claim 12 , wherein R 1 , R 3 , R 5 , and R 6 are C 11 alkyl; and R 2 and R 4 are C 13 alkyl.