Porous silicon drug-eluting particles
View Patent ↗The invention provides a biodegradable drug-eluting particle useful for the delivery of diagnostic or therapeutic agents. In certain embodiments, the drug-eluting particle of the invention comprises a biodegradable porous silicon body, a reservoir formed within the porous silicon body having at least one opening to an exterior of the body, wherein the reservoir contains a therapeutic or diagnostic agent, and an agent-permeable seal disposed over the at least one opening. The invention further provides a method for treating a patient to obtain a desired local or systemic physiological or pharmacological effect comprising administering a sustained release drug delivery particle of the invention. The invention also provides methods of fabricating a drug-eluting particle for releasing therapeutic agents.
1. A biodegradable drug-eluting particle comprising:
a porous silicon body;
a reservoir formed within the porous silicon body having at least one opening to an exterior of the body, wherein the reservoir has a diameter of at least about 120 μm;
a drug core within the reservoir wherein the drug core comprises a therapeutic or diagnostic agent; and
an agent-permeable seal disposed over the at least one opening.
2. The particle of claim 1 , wherein the agent-permeable seal provides for sustained release of the agent.
3. The particle of claim 1 , wherein the particle has at least two openings to an exterior of the body and an agent-permeable seal disposed over the at least two openings.
4. The particle of claim 3 , wherein the particle has a plurality of openings to an exterior of the body and one or more agent-permeable seals covering each of the plurality of openings.
5. The particle of claim 1 , wherein the particle has at least one dimension less than 1 mm.
6. The particle of claim 5 , wherein the particle has at least one dimension from 20-600 microns.
7. The particle of claim 6 , wherein the particle has at least one dimension from 100-500 microns.
8. The particle of claim 1 , wherein the porous silicon body is macroporous.
9. The particle of claim 1 , wherein the porous silicon body is mesoporous.
10. The particle of claim 1 , wherein the porous silicon body is microporous.
11. The particle of claim 1 , wherein the porous silicon body is essentially impermeable to the passage of the therapeutic or diagnostic agent.
12. The particle of claim 1 , wherein the porous silicon body has a porosity from 20% to 70%.
13. The particle of claim 1 , wherein the drug core comprises 0.01 to 50 mg of the agent.
14. The particle of claim 13 , wherein the drug core comprises from 0.05 to 20 mg of the agent.
15. The particle of claim 1 , wherein the drug core comprises a therapeutic agent.
16. The particle of claim 15 , wherein the therapeutic agent is for treating or preventing an ocular condition.
17. The particle of claim 16 , wherein the therapeutic agent is fluocinolone acetonide.
18. The particle of claim 1 , wherein the drug core comprises a diagnostic agent.
19. The particle of claim 18 , wherein the diagnostic agent is for ophthalmic use.
20. The particle of claim 1 , wherein the drug core comprises polyvinyl alcohol.
21. The particle of claim 1 , wherein the agent-permeable seal comprises polyvinyl alcohol.
22. The particle of claim 1 , wherein the particle is partially biodegradable in a patient.
23. The particle of claim 1 , wherein the particle is completely biodegradable in a patient.
24. The particle of claim 1 , wherein the particle has a lifespan of about 1 month.
25. The particle of claim 1 , wherein the particle has a lifespan of about 1 year.
26. The particle of claim 1 , wherein the reservoir has a diameter of about 120 μm to about 300 μm.
27. A method for treating a patient to obtain a desired local or systemic physiological or pharmacological effect comprising administering the biodegradable drug-eluting particle of claim 1 to a patient and allowing the agent to elute from the particle and come in direct contact with cells or tissues of the patient.
28. The method of claim 27 , comprising administering a plurality of particles in a single administration.
29. The method of claim 27 , wherein the particle is administered intraocularly.
30. A method for manufacturing biodegradable porous silicon particles, comprising:
providing a silicon wafer,
depositing and patterning a material on the wafer for use as an etch mask,
etching a plurality of reservoirs in the wafer, wherein each reservoir has a diameter of at least about 120 μm,
introducing pores into the silicon substrate,
filling the reservoirs with a drug core comprising a therapeutic or diagnostic agent, and
covering the reservoirs with one or more agent permeable seals.
31. The method of claim 30 , wherein etching a plurality of reservoirs in the wafer is performed prior to introducing pores into the silicon wafer.
32. The method of claim 30 , wherein introducing pores into the silicon wafer is performed prior to etching a plurality of reservoirs in the wafer.
33. The method of claim 30 , wherein the agent-permeable seal comprises a polymer.
34. The method of claim 30 , wherein the method further comprises subdividing the wafer through controlled partitioning into a number of discrete particles.