Implants for localized drug delivery and methods of use thereof

Patent metadata

Field	Value
Publication number	US-11324935-B2
Application number	US-201916273760-A
Country	US
Kind code	B2
Filing date	Feb 12, 2019
Priority date	Aug 19, 2014
Publication date	May 10, 2022
Grant date	May 10, 2022

Abstract

Provided herein is an implant for delivering a hydrophobic active agent to a target tissue. The implant may include a scaffold defining a first surface and a second surface opposite the first surface, wherein the scaffold is substantially impermeable to the hydrophobic active agent, and a silicone tubing having a wall permeable to the hydrophobic active agent, wherein a first length of the silicone tubing is affixed to the first surface of the scaffold, wherein two ends of the silicone tubing extend from the first surface, and wherein a path outlined by a second length of the silicone tubing within the first length is circuitous. Also provided is a method of using the implant to locally deliver the hydrophobic active agent to the target tissue, and kits that find use in performing the present method.

First claim

What is claimed is:

1. A method of treating prostate cancer in a subject, the method comprising:
implanting a depot in a prostate in said subject, wherein said depot comprises, prior to said implanting:
a biocompatible tubing having a wall devoid of any through-hole, first and second opposed ends formed from a portion of the wall of the biocompatible tubing, a lumen extending between the first and second opposed ends and defining a fully enclosed volume, said first and second opposed ends being sealed; and
a hormone-modulating active agent provided in the fully enclosed volume, wherein said biocompatible tubing is permeable to said hormone-modulating active agent and the only means for the hormone-modulating active agent to exit the fully enclosed volume is by diffusing through the wall of the biocompatible tubing including the portion of the wall forming the first and second opposed ends that are sealed, the depot delivering said hormone-modulating active agent to said prostate in said subject as said hormone-modulating active agent is released through said wall including the portion of the wall forming the first and second opposed ends of said biocompatible tubing when implanted in said prostate in said subject.

2. The method of claim 1 , wherein said depot is an elastomeric silicone tubing.

3. The method of claim 1 , wherein said hormone-modulating active agent is selected from the group consisting of a cholesterol, an estradiol, a progesterone, a testosterone, a corticosteroid, derivatives thereof, and synthetic analogs thereof.

4. The method of claim 1 , wherein said hormone-modulating active agent is present in said depot at a concentration of about 0.0001 mg to about 10 mg per cm of the depot.

5. The method of claim 1 , wherein said delivery of said hormone-modulating active agent to said prostate is at an average level of about 50 nM to about 1000 nM of said hormone-modulating active agent in said prostate.

6. The method of claim 1 , wherein a level of said hormone-modulating active agent in blood plasma is about 95% or less when compared to a level of said hormone-modulating active agent in said prostate.

7. The method of claim 1 , wherein said hormone-modulating active agent is present in a non-target tissue from a substantially undetectable level to about 10 nM.

8. The method of claim 1 , wherein said depot is configured to deliver said hormone-modulating active agent to said prostate for about 5 weeks to about 10 years.

9. The method of claim 1 , wherein the biocompatible tubing has an intertwined, double-helical form.

10. The method of claim 1 , further comprising a fill port attached to the biocompatible tubing.

11. The method of claim 1 , wherein said hormone-modulating active agent is selected from the group consisting of an anti-estrogen, an anti-androgen, a selective estrogen receptor modulator (SERM), and a selective estrogen receptor down-regulator.

12. A method of modulating hormone levels in a target tissue in a subject, the method comprising:
implanting a polymeric tubing in said target tissue,
wherein said polymeric tubing comprises, prior to said implanting:
first and second ends;
a lumen extending between the first and second ends;
a polymeric wall extending between the first and second ends, the polymeric wall fully surrounding the lumen and defining a fully enclosed volume; and
an active agent distributed throughout said polymeric wall, wherein said polymeric wall is permeable to said active agent, and the first and second ends are sealed such that the only means for the active agent to exit the polymeric tubing is by diffusing through the polymeric wall; and
the polymeric tubing directly delivering said active agent to said target tissue in said subject as said active agent is released through said polymeric wall of said polymeric tubing when implanted in said target tissue.

13. The method of claim 12 , wherein said active agent is a steroid.

14. The method of claim 12 , wherein said active agent lowers androgen levels.

15. The method of claim 12 , wherein said active agent is selected from the group consisting of an anti-estrogen, an anti-androgen, a selective estrogen receptor modulator (SERM), a selective estrogen receptor down-regulator, and an inhibitor of poly adenosine diphosphate (ADP) ribose polymerase (PARP).

16. The method of claim 12 , wherein said polymeric tubing is fabricated from a non-biodegradable material.

17. The method of claim 12 , wherein said target tissue comprises a breast tissue or a prostate tissue.

18. The method of claim 12 , wherein said active agent is present in said polymeric tubing at a concentration of about 0.0001 mg to about 10 mg per cm of the polymeric tubing.

19. The method of claim 12 , wherein after said implanting, an average level of said active agent in said target tissue is in a range of about 50 nM to about 1000 nM.

20. The method of claim 12 , wherein said active agent is present in a non-target tissue from a substantially undetectable level to about 10 nM.

21. The method of claim 12 , wherein said polymeric tubing delivers a sustained release of said active agent to said target tissue.

22. The method of claim 12 , wherein said polymeric tubing delivers said active agent to said tissue for about 5 weeks to about 10 years.

23. The method of claim 12 , wherein said polymeric wall comprises a polymer matrix and wherein said active agent is distributed throughout said polymer matrix.

24. The method of claim 12 , wherein the active agent is hydrophobic and the polymeric wall is permeable to the hydrophobic active agent.

25. The method of claim 12 , wherein the polymeric tubing has an intertwined, double-helical form.

Assignees

• Univ California

Inventors

• Munster Pamela
• Kiriakis Jim
• Sbitany Hani
• Thomas Scott

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/565

  not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol · CPC title

• A61K9/0041

  Mammary glands, e.g. breasts, udder; Intramammary administration · CPC title

• A61L27/54

  Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} · CPC title

• A61L27/18

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds · CPC title