Drug delivery device with intravesical tolerability
Intravesical devices are provided that are wholly deployable within the bladder of a patient in need of treatment and are well tolerated by the patient. The device may include an elastic body having a retention shape having (i) dimensions that provide intravesical mobility and that prevent voiding of the medical device through the urethra, and (ii) dimensions, buoyancy, or both, that exclude the medical device from entering the orifices of the ureters. The elastic body may exert a maximum acting force less than 1N when compressed to a shape with a maximum dimension in any dimension of 3 cm. The device may include a drug for controlled release within the bladder, for treatment of the bladder or a regional tissue. Methods of treatment are also provided that include selecting a patient in need of treatment in the bladder where tolerability of the treatment is a primary concern.
1. An intravesical drug delivery device, comprising:
an elongated elastic body comprising a drug reservoir lumen defined therein; and
a drug formulation disposed within the drug reservoir lumen, the drug formulation comprising a drug which comprises a kinase inhibitor,
wherein the elongated elastic body has a coiled retention shape having (i) dimensions that provide intravesical mobility and prevent voiding of the device through the urethra, and (ii) a maximum dimension in any direction of 6 cm or less when in an uncompressed state, and
wherein the device exerts a maximum acting force less than 1 N when the device is compressed from the retention shape to a shape having a maximum dimension in any direction of 3 cm or less.
2. The device of claim 1 , wherein the elongated elastic body comprises a silicone tube which comprises one or more apertures extending through a sidewall of the silicone tube, and wherein the device is configured to provide release of the drug through the one or more apertures, driven at least in part by an osmotic pressure in the drug reservoir lumen.
3. The device of claim 2 , wherein the one or more apertures have a diameter between 25 μm and 300 μm.
4. The device of claim 2 , wherein the one or more apertures have a diameter between 100 μm and 200 μm.
5. The device of claim 1 , wherein the elongated elastic body comprises a tube which comprises polyurethane.
6. The device of claim 1 , wherein the elongated elastic body has no apertures or passing pores, and the device is configured to release the drug by diffusion through a wall of the elastic body.
7. The device of claim 1 , wherein the drug formulation disposed within the drug reservoir lumen comprises between 10 and 100 mini-tablets.
8. The device of claim 1 , wherein the elongated elastic body comprises two integrally formed tubes, which define the drug reservoir lumen and a retention frame lumen.
9. The device of claim 8 , further comprising a nitinol wireform disposed within the retention frame lumen.
10. The device of claim 1 , wherein the device in the retention shape and uncompressed has a maximum dimension in any direction that is less than 10 cm.
11. The device of claim 1 , wherein the device in the retention shape and uncompressed has a maximum dimension in any direction that is less than 5 cm.
12. The device of claim 1 , wherein the device exerts a maximum acting force less than 1 N when the device is compressed from the retention shape to a shape with a maximum dimension in any direction of 1.5 cm.
13. A drug delivery device for deployment within the bladder of a human patient, the device comprising:
an elongated elastic body which comprises two integrally formed tubes, one of which defines a drug reservoir lumen and the other which defines a retention frame lumen;
a nitinol wireform disposed in the retention frame lumen; and
a drug formulation, comprising a drug, disposed within the drug reservoir lumen, wherein the drug formulation is in the form of a plurality of mini-tablets,
wherein the elongated elastic body has a coiled retention shape having (i) dimensions that provide intravesical mobility and prevent voiding of the device through the urethra, and (ii) a maximum dimension in any direction of 6 cm or less when in an uncompressed state, and
wherein the device exerts a maximum acting force less than 1 N when the device is compressed from the retention shape to a shape having a maximum dimension in any direction of 3 cm or less.
14. The device of claim 13 , wherein the drug comprises a kinase inhibitor.
15. The device of claim 14 , wherein the elastic body exerts a maximum acting force less than 1 N when compressed to a shape with a maximum dimension in any direction of 1.5 cm or less.
16. The device of claim 14 , wherein the tube defining the drug reservoir lumen comprises one or more apertures extending through a sidewall of said tube, wherein the device is configured to provide release of the drug through the one or more apertures, driven at least in part by an osmotic pressure in the drug reservoir lumen.
17. The device of claim 16 , wherein the one or more apertures consists of an aperture having a diameter between 25 μm and 300 μm.
18. The device of claim 16 , wherein the one or more apertures have a diameter between 100 μm and 200 μm.
19. The device of claim 16 , wherein the one or more apertures are in a sidewall position opposite from the tube defining the retention frame lumen.
20. The device of claim 14 , wherein the drug is a low solubility drug, the elongated elastic body has no apertures or passing pores, and the device is configured to release the drug by diffusion through a wall of the tube defining the drug reservoir lumen.
21. A drug delivery device, comprising:
an elongated elastic body comprising a first end, an opposed second end, a tubular intermediate portion disposed between the first and second ends, and a drug reservoir lumen defined within the tubular intermediate portion; and
a drug formulation disposed within the drug reservoir lumen, the drug formulation comprising a drug,
wherein the elongated elastic body has a coiled retention shape in which the first and second ends are inwardly directed, and
wherein the device exerts a maximum acting force less than 1 N when the device is compressed from the coiled retention shape to a shape having a maximum dimension in any direction of 3 cm.
22. The device of claim 21 , wherein the coiled retention shape has a maximum dimension in any direction of 6 cm or less when in an uncompressed state.
23. The device of claim 21 , further comprising a nitinol wireform which imparts the coiled retention shape to the elongated elastic body.
24. The device of claim 21 , wherein the elongated elastic body is configured to elastically deform to an insertion shape in which the first and second ends are directed away from another for deployment of the device through a deployment instrument insertable through a patient's urethra.
25. The device of claim 24 , wherein the insertion shape in substantially linear.
26. The device of claim 21 , wherein, in the coiled retention shape, the first and second end portions of the elastic body are relatively straight compared to the intermediate portion.
27. The device of claim 26 , further comprising a nitinol wireform which imparts the coiled retention shape to the elongated elastic body.
28. The device of claim 27 , wherein, in the coiled retention shape, the nitinol wireform has first and second end portions and a central portion therebetween, and the first and second end portions are relatively straight compared to the central portion.
29. The device of claim 21 , wherein the drug formulation is in the form of a plurality of mini-tablets.