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 1 N 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 system comprising:
a silicone body which comprises a drug reservoir lumen and a retention frame lumen, wherein the drug reservoir lumen includes a first sealed end and an opposed second sealed end, and a release aperture;
a plurality of mini-tablets disposed in the drug reservoir lumen, wherein at least some of the mini-tablets comprise at least 75% by weight of a drug which comprises gemcitabine or a salt form thereof, with the remainder of the weight of the at least some of the mini-tablets being one or more excipients; and
a retention frame disposed in the retention frame lumen, wherein the retention frame comprises a nitinol wire,
wherein the drug delivery system is deformable between a deployment shape for passage of the drug delivery system through a patient's urethra, and a retention shape having dimensions that provide intravesical mobility of the drug delivery system and that are configured to prevent voiding of the system through the urethra, and
wherein the drug delivery system has dimensions, buoyancy, or both, that are configured to preclude the drug delivery system from entering ureter orifices of the patient.
2 . The intravesical drug delivery system of claim 1 , which is configured to permit the plurality of mini-tablets to be solubilized in vivo and to release the gemcitabine, driven by osmotic pressure, through the release aperture, which is in a sidewall of the silicone body in fluid communication with the drug reservoir lumen.
3 . The intravesical drug delivery system of claim 1 , wherein the silicone body exerts a maximum acting force less than 1 N when the silicone body is compressed from the retention shape to a shape having a maximum dimension in any direction of 3 cm or less.
4 . The intravesical drug delivery system of claim 3 , wherein the drug delivery system exerts a maximum acting force less than 1 N when the drug delivery system is compressed from the retention shape to a shape with a maximum dimension in any direction of 1.5 cm.
5 . The intravesical drug delivery system of claim 1 , wherein the retention shape has a maximum dimension in any direction of 6 cm or less when the drug delivery system is in an uncompressed state.
6 . The intravesical drug delivery system of claim 1 , wherein the plurality of mini-tablets is between 10 and 100 mini-tablets, and wherein the plurality of mini-tablets are aligned in a row in the drug reservoir lumen.
7 . The intravesical drug delivery system of claim 1 , wherein the drug reservoir lumen has a cylindrical shape and wherein the at least some of the plurality of mini-tablets comprises 80% or more by weight of the drug.
8 . The intravesical drug delivery system of claim 1 , wherein the one or more excipients comprise a lubricant and a binder.
9 . The intravesical drug delivery system of claim 1 , wherein the silicone body comprises two integrally formed tubes that are substantially aligned and adjoined along a longitudinal edge, wherein one of the tubes defines the retention frame lumen and the other one of the tubes defines the drug reservoir lumen.
10 . An intravesical drug delivery system comprising:
a water-permeable polymeric body which comprises a drug reservoir lumen and a retention frame lumen integrally formed with the drug reservoir lumen, wherein the drug reservoir lumen includes a first sealed end and an opposed second sealed end;
a plurality of mini-tablets disposed in the drug reservoir lumen, wherein the mini-tablets comprise (i) a drug which comprises a fibroblast growth factor receptor-3 (FGFR3)-selective tyrosine kinase inhibitor, and (ii) one or more excipients; and
a retention frame disposed in the retention frame lumen, wherein the retention frame comprises a nitinol wire,
wherein the drug delivery system is deformable between a deployment shape for passage of the drug delivery system through a patient's urethra, and a retention shape having dimensions that provide intravesical mobility of the drug delivery system and that are configured to prevent voiding of the drug delivery system through the urethra, and
wherein the drug delivery system has dimensions, buoyancy, or both, that are configured to preclude the drug delivery system from entering ureter orifices of the patient.
11 . The intravesical drug delivery system of 10 , which is configured to permit the plurality of mini-tablets to be solubilized in vivo and to release the FGFR3-selective tyrosine kinase inhibitor, by diffusion through a wall of the polymeric body bounding the drug reservoir lumen.
12 . The intravesical drug delivery system of claim 10 , wherein the polymeric body exerts a maximum acting force less than 1 N when the polymeric body is compressed from the retention shape to a shape having a maximum dimension in any direction of 3 cm or less.
13 . The intravesical drug delivery system of claim 12 , wherein the drug delivery system exerts a maximum acting force less than 1 N when the drug delivery system is compressed from the retention shape to a shape with a maximum dimension in any direction of 1.5 cm
14 . The intravesical drug delivery system of claim 10 , wherein the retention shape has a maximum dimension in any direction of 6 cm or less when the drug delivery system is in an uncompressed state.
15 . The intravesical drug delivery system of claim 10 , wherein the plurality of mini-tablets is between 10 and 100 mini-tablets, and wherein the plurality of mini-tablets are aligned in a row in the drug reservoir lumen.
16 . The intravesical drug delivery system of claim 10 , wherein the mini-tablets comprise 50% or more by weight of the drug.
17 . The intravesical drug delivery system of claim 10 , wherein the one or more excipients comprises a lubricant and a binder.
18 . The intravesical drug delivery system of claim 10 , wherein the drug reservoir lumen has a cylindrical shape.
19 . The intravesical drug delivery system of claim 10 , wherein the polymeric body comprises two integrally formed tubes that are substantially aligned and adjoined along a longitudinal edge, wherein one of the tubes defines the retention frame lumen and the other one of the tubes defines the drug reservoir lumen.