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 drug delivery carrier comprising:
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 the silica body and stably sealing the plurality of pores, wherein the 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 the silica body, wherein the first therapeutic agent comprises gemcitabine; and
a second therapeutic agent disposed in the lipid bilayer, wherein the second therapeutic agent comprises paclitaxel.
2. The drug delivery carrier of claim 1 , wherein the drug delivery carrier provides a predetermined dose and ratio of first therapeutic agent to second therapeutic agent.
3. The drug delivery carrier of claim 1 , wherein the first therapeutic agent and the second therapeutic agent act synergistically.
4. The drug delivery carrier of claim 1 , wherein the drug delivery carrier includes about 20% w/w or greater of gemcitabine molecules within the pores of the silica body.
5. The drug delivery carrier of claim 1 , wherein the drug delivery carrier includes about 30% w/w or greater of gemcitabine molecules within the pores of the silica body.
6. The drug delivery carrier of claim 1 , wherein the drug delivery carrier includes about 40% w/w or greater of gemcitabine molecules within the pores of the silica body.
7. The drug delivery carrier of claim 1 , wherein the lipid bilayer is formed from a lipid film containing the second therapeutic agent.
8. The drug delivery carrier of claim 1 , wherein the drug delivery carrier is configured to retain the first therapeutic agent within the silica body without substantial loss for at least 1 week prior to administration to a subject.
9. The drug delivery carrier of claim 1 , wherein the drug delivery carrier is configured to retain the first therapeutic agent within the silica body with 10% or less loss for at least 1 week prior to administration to a subject.
10. The drug delivery carrier of claim 1 , wherein the drug delivery carrier is a member of a monodisperse population of drug delivery carriers.
11. The drug delivery carrier of claim 1 , wherein the drug delivery carrier is a submicron structure with a maximum dimension of between 20 nm and 300 nm.
12. The drug delivery carrier of claim 1 , wherein the drug delivery carrier has a submicron structure with a maximum dimension of between 50 nm and 200 nm.
13. The drug delivery carrier of claim 1 , wherein the lipid bilayer comprises a phospholipid bilayer.
14. The drug delivery carrier of claim 13 , wherein the phospholipid bilayer comprises 2-dioleoyl-3-trimethylammonium-propane (DOTAP), 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS),1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), or any combination thereof.
15. A composition comprising a plurality of drug delivery carriers, each drug delivery carrier comprising:
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 the silica body and stably sealing the plurality of pores, wherein the 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 the silica body, wherein the first therapeutic agent comprises gemcitabine; and
a second therapeutic agent disposed in the lipid bilayer, wherein the second therapeutic agent comprises paclitaxel.
16. The composition of claim 15 , wherein the composition comprises a stable colloidal suspension.
17. The composition of claim 15 , wherein the plurality of drug delivery carriers provides a predetermined dose and ratio of the first therapeutic agent to the second therapeutic agent.
18. The composition of claim 15 , wherein the plurality of drug delivery carriers form a monodisperse population having a deviation in average diameter of 10% or less.
19. The composition of claim 15 , wherein the composition is formulated for systemic administration to a subject for treating cancer.
20. The composition of claim 15 , wherein the composition is formulated for intravenous, intra-arterial, intraperitoneal, intramuscular, or subcutaneous administration.