Shape changing drug delivery devices and methods
Drug delivery using bio-affecting drugs, particularly with shape changing drug delivery devices. Embodiments are included for depots for delivery of a therapeutic agent that change from an elongated state ex vivo to a coil in vivo where the agent is released.
1. A device for drug delivery comprising a therapeutic agent disposed in a solid vehicle that comprises a first xerogel and a second xerogel, wherein the first xerogel is a rod and the second xerogel is a layer on the first xerogel, wherein the first xerogel and the second xerogel differentially swell and/or elongate in physiological solution to change the rod into a curve shape in response to a phosphate buffered saline (PBS) at 37° C., pH 7.4, wherein the solid vehicle provides a controlled release of the therapeutic agent.
2. The device of claim 1 wherein the solid vehicle has an aspect ratio of at least 1:10.
3. The device of claim 1 wherein the first xerogel has a first coefficient of elongation and/or a first coefficient of swelling in aqueous solution and the second xerogel has a second coefficient of elongation and/or a second coefficient of swelling in aqueous solution, with the first and the second coefficients being different.
4. The device of claim 3 wherein the curve shape comprises a coil.
5. The device of claim 4 with the solid vehicle forming the coil within 30 seconds of introduction to PBS at 37° C., pH 7.4.
6. The device of claim 1 wherein, in a cross-section taken perpendicular to a central axis of the rod, the second material xerogel has a larger cross-sectional area than a cross-sectional area of the first xerogel, as measured in PBS at 37° C., pH 7.4.
7. The device of claim 6 wherein a ratio of the cross-sectional area of the second xerogel to the cross-sectional area of the first xerogel is at least 1:1 and is no more than 5:1.
8. The device of claim 6 wherein the first xerogel is eccentrically coaxial within the second xerogel.
9. The device of claim 1 wherein the first xerogel has a first coefficient of elongation in aqueous solution and the second xerogel has a second coefficient of elongation in aqueous solution, wherein the first coefficient of elongation is less than 1 and the second coefficient of elongation is at least 1.
10. The device of claim 9 wherein the first coefficient of elongation is from 0.1 to 0.5 and the second coefficient of elongation is from 1 to 10.
11. The device of claim 1 wherein the first xerogel has a first coefficient of swelling in aqueous solution and the second xerogel has a second coefficient of swelling in aqueous solution, wherein the first coefficient of swelling is less than the second coefficient of swelling.
12. The device of claim 11 wherein the first coefficient of swelling is from 1.0 to 2.0 and the second coefficient of swelling is from 2.0 to 10.
13. The device of claim 1 wherein the first xerogel and the second material degrade in PBS at 37° C., pH 7.4, at a rate independently selected from 2 days to 5 years.
14. The device of claim 1 wherein the first xerogel comprises at least a first crosslinked polymer and the second xerogel comprises at least a second crosslinked polymer.
15. The device of claim 1 wherein the first xerogel and the second xerogel are independently selected from the group consisting of natural, synthetic, and biosynthetic polymers.
16. The device of claim 1 wherein the xerogel and the second xerogel are joined by covalent bonds.
17. The device of claim 1 wherein the therapeutic agent has a solubility in aqueous solution of no more than 10 micrograms per milliliter, is a protein with MW greater than 1000 Da, or is encapsulated in a microparticle.
18. The device of claim 1 wherein the therapeutic agent comprises an anti-angiogenic agent, a tyrosine kinase inhibitor, anti-VEGF agent, an anti-PDGF agent, anti-Ang2 agent, steroid, antibiotic, or NSAID.
19. The device of claim 1 wherein the vehicle is a first vehicle, the rod is a first rod, the therapeutic agent is a first therapeutic agent, further comprising a second vehicle that comprises a third xerogel and a fourth xerogel, wherein the third xerogel is a second rod and the fourth xerogel is a layer on the third xerogel, wherein the third xerogel and the fourth xerogel differentially swell and/or elongate to curl the second rod into a curved shape in response to a physiological solution.
20. The device of claim 19 wherein the first therapeutic agent and the second therapeutic agent are an identity with each other.
21. The device of claim 19 wherein the first rod and the second rod are identical in length before placement into physiological solution.
22. The device of claim 19 wherein the first rod and the second rod are different in length before placement into physiological solution.
23. The device of claim 19 further comprising an applicator wherein the first vehicle and the second vehicle are disposed end to end relative to each other in the applicator.
24. The device of claim 23 wherein the first vehicle and/or the second vehicle comprise an end that is cut at an angle of 30-60 degrees relative to a perpendicular cross-section.
25. The device of claim 19 further comprising a third vehicle that comprises a fifth xerogel and a sixth xerogel, wherein the fifth xerogel is a third rod and the sixth xerogel is a layer on the fifth xerogel, wherein the fifth xerogel and the sixth xerogel differentially swell and/or elongate to curl the third rod into a curved shape in response to a physiological solution.