Substrate delivery of embedded liposomes
This invention relates to compositions useful for localized and sustained release of therapeutic agents, and more particularly to functionalized liposomes embedded in a polyelectrolyte multilayer. Methods of preparing the compositions, methods of treating diseases, devices, and pharmaceutical compositions comprising the compositions are also provided.
1. A method of treating a disease in a subject in need thereof, comprising administering to the subject a composition comprising:
i) one or more hyaluronic acid conjugated liposomes; and
ii) a polyelectrolyte multilayer, and
wherein the liposome comprises one or more therapeutic agents.
2. The method of claim 1 , wherein the composition releases the one or more therapeutic agents as a controlled release.
3. The method of claim 1 , wherein the composition releases the one or more therapeutic agents as a delayed release.
4. The method of claim 1 , wherein the disease is a cancer selected from the group consisting of pancreatic cancer, bladder cancer, brain cancer, breast cancer, colon cancer, endometrial cancer, gastrointestinal cancer, a hematological cancer, liver cancer, lung cancer, prostate cancer, skin cancer, stomach cancer, and renal cancer.
5. The method of claim 4 , wherein the cancer is breast cancer.
6. The method of claim 4 , wherein the cancer is brain cancer.
7. The method of claim 6 , wherein the brain cancer is glioblastoma.
8. The method of claim 1 , wherein the hyaluronic acid is conjugated on the surface of the liposome.
9. The method of claim 1 , wherein the one or more hyaluronic acid conjugated liposomes are deposited onto the polyelectrolyte multilayer.
10. The method of claim 1 , wherein the polyelectrolyte multilayer comprises one or more independently selected polycationic polymers.
11. The method of claim 1 , wherein the polyelectrolyte multilayer comprises one or more independently selected polyanionic polymers.
12. The method of claim 1 , wherein the polyelectrolyte multilayer comprises from about 2 to about 10 monolayers of poly-L-lysine (PLL) and from about 2 to about 10 monolayers of poly(sodium styrene sulfonate) (SPS).
13. The method of claim 1 , wherein each of the therapeutic agents is independently selected from the group consisting of a chemotherapeutic agent, a silencing RNA, a steroid, an immunosuppressant, an anti-microbial agent, an anti-fungal agent, an anti-inflammatory agent, a gene therapy agent, an anti-angiogenic agent, and a CRISPR/Cas9 agent.
14. The method of claim 13 , wherein the CRISPR/Cas9 agent is selected from Cre recombinase, TALE, and Cas9 based transcription factors.
15. The method of claim 13 , wherein at least one of the one or more therapeutic agents is a chemotherapeutic agent.
16. The method of claim 15 , wherein the chemotherapeutic agent comprises one or more oncolytic virus strains or particles.
17. The method of claim 13 , wherein the disease is an inflammatory disorder and at least one of the one or more therapeutic agents is an anti-inflammatory agent.
18. The method of claim 17 , wherein the anti-inflammatory agent comprises one or more virus strains or particles useful as a vaccine for treating the inflammatory disease or disorder.
19. The method of claim 13 , wherein the disease is an autoimmune disorder and at least one of the one or more therapeutic agents is an immunosuppressant agent.
20. The method of claim 19 , wherein the immunosuppressant agent comprises one or more virus strains or particles useful as a vaccine for treating the autoimmune disease or disorder.