Local drug delivery devices and methods for treating cancer

Patent metadata

Field	Value
Publication number	US-11167066-B2
Application number	US-201615055012-A
Country	US
Kind code	B2
Filing date	Feb 26, 2016
Priority date	Apr 10, 2013
Publication date	Nov 9, 2021
Grant date	Nov 9, 2021

Abstract

Drug-eluting devices and methods for the treatment of tumors of the pancreas, biliary system, gallbladder, liver, small bowel, or colon, are provided. Methods include deploying a drug-eluting device having a film which includes a mixture of a degradable polymer and a chemotherapeutic drug, wherein the film has a thickness from about 2 μm to about 1000 μm, into a tissue site and releasing a therapeutically effective amount of the chemotherapeutic drug from the film to treat the tumor, wherein the release of the therapeutically effective amount of the drug from the film is controlled by in vivo degradation of the polymer at the tissue site.

First claim

We claim:

1. A method of treating a tumor of the pancreas, biliary system, gallbladder, liver, small bowel, or colon, comprising:
deploying a drug-eluting device into a biliary or pancreatic duct of a patient in need of treatment, the device comprising:
a film which forms an outer surface of the device and comprises a mixture of a degradable polymer consisting of poly(lactic-co-glycolic acid) and a chemotherapeutic drug in which the chemotherapeutic drug is homogenously distributed in the poly(lactic-co-glycolic acid) via solvent evaporation of a solution of the chemotherapeutic drug and the poly(lactic-co-glycolic acid) wherein the film is formed from a solution containing poly(lactic-co-glycolic acid) in an amount of from 10 to 30 percent weight by volume, wherein the film has a uniform thickness from 10 μm to 100 μm and is configured to provide release of the chemotherapeutic drug via degradation of the poly(lactic-co-glycolic acid); and
a biocompatible substratum to which the film is adhered, the substratum comprising a stent; and

releasing a therapeutically effective amount of the chemotherapeutic drug from the film to treat the tumor,
wherein the release of the therapeutically effective amount of the chemotherapeutic drug from the film is controlled by in vivo degradation of the poly(lactic-co-glycolic acid) in the biliary or pancreatic duct,
wherein the release of the therapeutically effective amount of the chemotherapeutic drug from the film follows a delay period of from about 2 days to about 14 days after deploying the device into the biliary or pancreatic duct, wherein a sub-therapeutically effective amount of the drug or no drug is released during the delay period, and
wherein the delay period is controlled solely by the in vivo degradation of the poly(lactic-co-glycolic acid) in the biliary or pancreatic duct.

2. The method of claim 1 , wherein the release of the therapeutically effective amount of the chemotherapeutic drug, after the delay period, has an initial release rate that is substantially linear for at least 3 days.

3. The method of claim 1 , wherein the delay period is from 2 to 4 days.

4. The method of claim 1 , wherein the chemotherapeutic drug is selected from the group consisting of paclitaxel, gemcitabine, nab-paclitaxel, 5-fluorouracil, oxaliplatin, irinotecan, and combinations thereof.

5. The method of claim 1 , wherein the chemotherapeutic drug is paclitaxel.

6. The method of claim 5 , wherein the therapeutically effective amount of the paclitaxel released is at least about 1 mg/day.

7. The method of claim 5 , wherein the therapeutically effective amount of the paclitaxel released is at a mean average amount of from 5 mg/day to 125 mg/day.

8. The method of claim 5 , wherein the therapeutically effective amount of paclitaxel is released over a treatment period from about 10 days to about 90 days.

9. The method of claim 1 , wherein the mixture comprises from about 1 wt % to about 10 wt % of paclitaxel.

10. The method of claim 1 , wherein the poly(lactic-co-glycolic acid) is configured to degrade within a period from about 2 days to about 12 months after deployment.

11. A method of treating a tumor of the pancreas, biliary system, gallbladder, liver, small bowel, or colon, comprising:
deploying a drug-eluting device into a tissue site of the pancreas, biliary system, gallbladder, liver, small bowel, or colon of a patient in need of treatment, the device comprising:
a film which forms an outer surface of the device and comprises a mixture of a degradable polymer consisting of poly(lactic-co-glycolic acid) and a chemotherapeutic drug in which the chemotherapeutic drug is homogenously distributed in the poly(lactic-co-glycolic acid), via solvent evaporation of a solution of the chemotherapeutic drug and the poly(lactic-co-glycolic acid) wherein the film is formed from a solution containing poly(lactic-co-glycolic acid) in an amount of from 10 to 30 percent weight by volume, wherein the film has a uniform thickness from 10 μm to 100 μm, and is configured to provide release of the chemotherapeutic drug via degradation of the poly(lactic-co-glycolic acid); and
a biocompatible substratum to which the film is adhered, the substratum comprising a stent; and

releasing a therapeutically effective amount of the chemotherapeutic drug from the film to treat the tumor,
wherein the release of the therapeutically effective amount of the chemotherapeutic drug from the film is controlled by in vivo degradation of the poly(lactic-co-glycolic acid) in the tissue site,
wherein the release of the therapeutically effective amount of the chemotherapeutic drug from the film follows a delay period of from 2 days to 14 days after the deploying the device in the tissue site, wherein a sub-therapeutically effective amount of the drug or no drug is released during the delay period, and
wherein the delay period is controlled solely by the in vivo degradation of the poly(lactic-co-glycolic acid) in the tissue site.

12. The method of claim 11 , wherein deploying the drug-eluting device comprises implanting the device in the patient in an open surgical procedure or laparoscopically.

13. The method of claim 12 , wherein the tissue site is a biliary or pancreatic duct and the device is configured to prevent closure of the duct in which it is deployed.

14. The method of claim 11 , wherein the release of the therapeutically effective amount of the chemotherapeutic drug, after the delay period, has an initial release rate that is substantially linear for at least 3 days.

15. The method of claim 11 , wherein the delay period is from 2 to 4 days.

16. The method of claim 11 , wherein the in vivo degradation of the poly(lactic-co-glycolic acid) is hydrolytic degradation.

17. The method of claim 11 , wherein the chemotherapeutic drug is selected from the group consisting of paclitaxel, gemcitabine, nab-paclitaxel, 5-fluorouracil, oxaliplatin, irinotecan, and combinations thereof.

18. The method of claim 11 , wherein the chemotherapeutic drug is paclitaxel.

19. The method of claim 18 , wherein the therapeutically effective amount of the paclitaxel released is at least about 1 mg/day.

20. The method of claim 18 , wherein the therapeutically effective amount of the paclitaxel released is at a mean average amount of from 5 mg/day to 125 mg/day.

21. The method of claim 18 , wherein the therapeutically effective amount of paclitaxel is released over a treatment period from about 10 days to about 90 days.

22. The method of claim 11 , wherein the mixture comprises from about 1 wt % to about 10 wt % of paclitaxel.

23. The method of claim 11 , wherein the degradable polymer is configured to degrade within a period from about 2 days to about 12 months after deployment,
deploying a drug-eluting device into a tissue site of the pancreas, biliary system, gallbladder, liver, small bowel, or colon of a patient in need of treatment, the device comprising:
a film which comprises a mixture of a degradable polymer, which consists of poly(lactic-co-glycolic acid), and paclitaxel distributed in the degradable polymer via solvent evaporation of a solution of the paclitaxel and the degradable polymer, wherein the film has a thickness from about 2 μm to about 1000 μm and is configured to release at least about 1 mg/day of the paclitaxel from the film by in vivo degradation of the polymer upon deployment at the tissue site; and
a biocompatible substratum to which the film is adhered, the s

Assignees

• Massachusetts Inst Technology
• Massachusetts Gen Hospital

Inventors

• Indolfi Laura
• Edelman Elazer R
• Langer Robert S
• Clark Jeffrey W
• Ting David T
• Ferrone Cristina Rosa Annamaria
• Ligorio Matteo

Classifications

• A61L2300/416

  Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus · CPC title

• A61P1/00

  Drugs for disorders of the alimentary tract or the digestive system · CPC title

• A61K47/34

  Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence) · CPC title

• A61K31/337

  having four-membered rings, e.g. taxol · CPC title

• A61L31/10 Primary

  Macromolecular materials · CPC title