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 composition comprising a first xerogel, a second xerogel, and a therapeutic agent, wherein
the first xerogel is in the form of a rod and the second xerogel is disposed as a layer on the first xerogel;
the first xerogel and second xerogel differentially swell or elongate in physiological solution to form, together, a curve or coil shape; and
the therapeutic agent is released in a controlled manner.
2. The composition of claim 1 , wherein the first xerogel has a first coefficient of elongation in physiological solution and the second xerogel has a second coefficient of elongation, wherein the first and the second coefficients are different.
3. The composition of claim 2 , wherein the first coefficient of elongation is less than 1 and the second coefficient of elongation is at least 1.
4. The composition of claim 2 , wherein the first coefficient of elongation is from 0.1 to 0.5 and the second coefficient of elongation is from 1 to 10.
5. The composition of claim 1 , wherein the first xerogel has a first coefficient of swelling in physiological solution and the second xerogel has a second coefficient of swelling in physiological solution, wherein the first and the second coefficients are different.
6. The composition of claim 5 , 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.
7. The composition of claim 1 , wherein with the first and second xerogel form said curve or said coil within 30 seconds of introduction to physiological solution.
8. The composition of claim 1 , wherein, in a cross-section taken perpendicular to a central axis of the first xerogel, the second xerogel has a larger cross-sectional area than a cross-sectional area of the first xerogel.
9. The composition of claim 8 , 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.
10. The composition of claim 1 , wherein the first xerogel and the second xerogel degrade in physiological solution at a rate independently selected from 2 days to 5 years.
11. The composition 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.
12. The composition of claim 1 , wherein the first xerogel and the second xerogel are independently selected from natural, synthetic, and biosynthetic polymers.
13. The composition of claim 1 , wherein the first xerogel and the second xerogel are joined by covalent bonds.
14. The composition of claim 1 , wherein the first xerogel comprises a first precursor cross-linked to a second precursor.
15. The composition of claim 14 , wherein the first precursor comprises polyethylene glycol repeats.
16. The composition of claim 14 , wherein the second precursor comprises polyethylene glycol repeats.
17. The composition of claim 1 , wherein the second xerogel comprises a first precursor cross-linked to a second precursor.
18. The composition of claim 17 , wherein the first precursor comprises polyethylene glycol repeats.
19. The composition of claim 17 , wherein the second precursor comprises polyethylene glycol repeats.
20. The composition of claim 1 , wherein the therapeutic agent has a solubility in aqueous solution of no more than 10 micrograms per milliliter.
21. The composition of claim 1 , wherein the therapeutic agent is an anti-angiogenic agent, a tyrosine kinase inhibitor, anti-VEGF agent, an anti-PDGF agent, an anti-Ang2 agent, a steroid, an antibiotic, or an NSAID.
22. The composition of claim 1 , wherein the therapeutic agent is a tyrosine kinase inhibitor.
23. The composition of claim 1 , wherein the therapeutic agent is axitinib.
24. A device for drug delivery comprising the composition according to claim 1 .