Lipid bilayer coated mesoporous silica nanoparticles with a high loading capacity for one or more anticancer agents
A submicron structure comprising a silica body defining a plurality of pores that are suitable to receive molecules therein, and having a surface, and a phospholipid bilayer coating the surface, wherein said submicron structure has a maximum dimension of less than one micron, and wherein the phospholipid bilayer stably seals the plurality of pores; and wherein the submicron structure is a member of a monodisperse population of submicron structures.
1. A method of treating a cancer in a subject, said method comprising:
administering to said subject an effective amount of a composition comprising a plurality of drug delivery carriers, wherein said drug delivery carriers each comprise:
a silica body having a plurality of pores suitable to receive a therapeutic agent therein, and having a surface;
an intact lipid bilayer coating the surface and encapsulating said silica body and stably sealing said plurality of pores, wherein said encapsulating is performed without lipid phase exchange and without contacting a preformed liposome with the silica body;
a first therapeutic agent within the pores of said silica body where said first therapeutic agent comprises gemcitabine; and
a second therapeutic agent disposed in said lipid bilayer where said second therapeutic agent comprises paclitaxel;
wherein said drug delivery carriers provide a predetermined dose and ratio of first therapeutic agent to second therapeutic agent, said plurality of drug delivery carriers form a monodisperse population of drug delivery carriers; and
wherein said drug delivery carriers have a maximum dimension that ranges from 20 nm to 300 nm.
2. The method of claim 1 , wherein said first therapeutic agent and said second therapeutic agent act synergistically.
3. The method of claim 1 , wherein the drug delivery carriers include about 20% w/w or greater of gemcitabine molecules within the pores of said silica body.
4. The method of claim 1 , wherein the drug delivery carriers include about 30% w/w or greater of gemcitabine molecules within the pores of said silica body.
5. The method of claim 1 , wherein the drug delivery carriers include about 40% w/w or greater of gemcitabine molecules within the pores of said silica body.
6. The method of claim 1 , wherein said drug delivery carriers are administered to a subject systemically.
7. The method of claim 1 , wherein said cancer comprises a cancer of a stroma.
8. The method of claim 7 , wherein said cancer is selected from the group consisting of pancreatic ductal adenocarcinoma (PDAC), prostate cancer, and glioblastoma.
9. The method of claim 8 , wherein said cancer is PDAC.
10. The method of claim 1 , wherein said administration is intravenous or intraarterial administration.
11. The method of claim 1 , wherein said monodisperse population show a deviation in average diameter of 10% or less.
12. The method of claim 1 , wherein said lipid bilayer is formed from a lipid film containing said second therapeutic agent.
13. The method of claim 1 , wherein said drug delivery carriers retain said first therapeutic agent within said silica body without substantial loss for at least 1 week prior to administration to a subject.
14. The method of claim 1 , wherein said drug delivery carriers retain said first therapeutic agent within said silica body with 10% or less loss for at least 1 week prior to administration to a subject.
15. The method of claim 1 , wherein said composition comprises a stable colloidal suspension.
16. The method of claim 1 , wherein said drug delivery carriers have a maximum dimension that ranges from 50 nm to 200 nm.