Methods for fabricating nano and microparticles for drug delivery
View Patent ↗The present invention generally relates to stimuli-responsive drug carriers and methods for making. More specifically, the present invention relates to stimuli-responsive lidded particles that respond to a physiological stimulus and dissolve at a target site inside the body thereby releasing therapeutic agents. The present invention further relates to solid, drug-loaded particles that are made from biodegradable polymers. The present invention further relates to methods for fabricating lidded particles and particles for drug delivery.
1. A method for making a plurality of monodisperse, solid particles comprising:
placing, on a silicon substrate, a patternable biodegradable polymer comprising a therapeutic agent, an imaging contrast agent, or both incorporated into a polymer matrix of the polymer;
placing a release layer on an imprint template;
imprinting the polymer by pressing the release layer and imprint template into the polymer, thereby forming a plurality of monodisperse, solid particles between 50 nm and 1000 nm in size corresponding to a plurality of particle-shaped portions of the imprint template and containing the therapeutic agent, an imaging contrast agent, or both, and also forming a residual polymer layer on the silicon substrate;
removing the imprint template;
oxygen plasma cleaning the plurality particles and residual polymer layer on the silicon substrate to remove the residual polymer layer; and
releasing the plurality of particles.
2. The method of claim 1 , further comprising forming the imprint template using e-beam lithography, reactive ion etching, or both.
3. The method of claim 1 , wherein the polymer comprises a compound comprising, polyethylene glycol functionalized peptide, biodegradable photocrosslinkable polymers, biodegradable acrylate functionalized polymers, poly(D,L-lactide-co-glycolide), polylactic acid, polyglycolic acid, polycaprolactone, polyethylene glycol, or a combination thereof.
4. The method of claim 1 , wherein imprinting comprises applying pressure and heat to the imprint template.
5. The method of claim 1 , wherein the imaging contrast agent comprises an MRI imaging agent.
6. The method of claim 1 , wherein the imaging contrast agent comprises a quantum dot or a gold nanoparticle.
7. The method of claim 1 , wherein releasing the plurality of particles comprises releasing with water.
8. The method of claim 1 , wherein placing the patternable biodegradable polymer on the silicon substrate comprises spin-coating.
9. The method of claim 1 , wherein the imprint template is pressed into the polymer and removed from the polymer with a micromanipulator.
10. The method of claim 1 , wherein the imprint has a depth of 200 nm.
11. The method of claim 1 , wherein the monodisperse, solid particles are from 50 nm to 300 nm in size.
12. A method for making a plurality of monodisperse, solid particles comprising:
placing, on a silicon substrate, a patternable biodegradable polymer comprising a therapeutic agent, an imaging contrast agent, or both incorporated into a polymer matrix of the polymer;
placing a release layer on an imprint template;
imprinting the polymer by pressing the release layer and imprint template into the polymer, thereby forming a plurality of monodisperse, solid particles between 50 nm and 1000 nm in size corresponding to a plurality of particle-shaped portion of the imprint template and containing the therapeutic agent, an imaging contrast agent, or both, and also forming a residual polymer layer on the silicon substrate;
removing the imprint template;
oxygen plasma cleaning the plurality particles and residual polymer layer on the silicon substrate to remove the residual polymer layer; and
releasing the plurality of particles,
wherein the biodegradable polymer is sensitive to a biomolecule, light, a magnetic field, ultrasound, pH or temperature, resulting in release the therapeutic agent.
13. The method of claim 12 , further comprising forming the imprint template using e-beam lithography, reactive ion etching, or both.
14. The method of claim 12 , wherein the polymer comprises a compound comprising, polyethylene glycol functionalized peptide, biodegradable photocrosslinkable polymers, biodegradable acrylate functionalized polymers, poly(D,L-lactide-co-glycolide), polylactic acid, polyglycolic acid, polycaprolactone, polyethylene glycol, or a combination thereof.
15. The method of claim 12 , wherein imprinting comprises applying pressure and heat to the imprint template.
16. The method of claim 12 , wherein the imaging contrast agent comprises an MRI imaging agent.
17. The method of claim 12 , wherein the imaging contrast agent comprises a quantum dot or a gold nanoparticle.
18. The method of claim 12 , wherein releasing the plurality of particles comprises releasing with water.
19. The method of claim 12 , wherein placing the patternable biodegradable polymer on the silicon substrate comprises spin-coating.
20. The method of claim 12 , wherein the imprint template is pressed into the polymer and removed from the polymer with a micromanipulator.
21. The method of claim 12 , wherein the imprint has a depth of 200 nm.
22. The method of claim 12 , wherein the monodisperse, solid particles are from 50 nm to 300 nm in size.