Methods and compositions for enhancing delivery of therapeutic agents to tissues

• US 7,217,735 B1
• Filed: 04/07/2000
• Issued: 05/15/2007
• Est. Priority Date: 04/09/1999
• Status: Expired due to Fees

• Current Assignee: Guillaume Wientjes, Jessie L.-S. Au
• Original Assignee: Guillaume Wientjes, Jessie L.-S. Au
• Inventors: Au, Jessie L.-S., Wientjes, Guillaume
• Primary Examiner(s): Yu; Misook
• Application Number:
  US09/547,825
• Time in Patent Office: 2,594 Days
• Field of Search: 424/457, 424/233.1
• US Class Current: 514/456
• CPC Class Codes: A61K 31/415 1,2-Diazoles
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/1272 with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids with cholesterol as the only non-phosphatidyl surfactant A61K9/127; lipids as modifying agent A61K47/543
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61K 9/5153 Polyesters, e.g. poly(lactide-co-glycolide)

Abstract

The invention, at least in part, is directed to methods for enhancing delivery of therapeutic agents, such as macromolecules and drugs, into the interior of tissues, such as solid tissues or tumors. The method initially uses an apoptosis inducing agent, such as paclitaxel, in doses which create channels within the tissues, and enhance the penetration of therapeutic agents to the interior of the tissue. Current methods of treating tissues are often not effective because the therapeutic agents are not delivered to the interior of the tissue. By using the methods and the compositions of the current invention, therapeutic agents can be delivered to the interior of the tissue.

Claims

1. A method for delivering a therapeutic agent to a tumor in a patient, which comprises the steps of:

(a) administering a dose of an apoptosis inducing agent paclitaxel to a patient having a tumor;

(b) allowing a time ranging from between about 24 and about 96 hours to elapse for said apoptosis inducing agent to induce greater than about 20% reduced cell density in the tumor; and

(c) administering a dose of a therapeutic agent to said patient, such that the therapeutic agent is delivered to the tumor to a greater extent than if administered without said apoptosis inducing agent.

2. The method of claim 1, wherein said therapeutic agent comprises a gene therapy construct, a protein bound drug, a chemotherapeutic agent, or an antibiotic.

3. The method of claim 2, wherein said therapeutic agent is a gene therapy construct, wherein said construct comprises a tumor suppressor gene.

4. The method of claim 3, wherein said tumor suppressor gene is p53.

5. The method of claim 1, wherein said therapeutic agent is a protein bound drug.

6. The method of claim 1, wherein said apoptosis inducing agent is administered systemically.

7. The method of claim 1, wherein said apoptosis inducing agent is administered regionally.

8. The method of claim 1, wherein said apoptosis inducing agent is administered locoregionally.

9. The method of claim 1, wherein said apoptosis inducing agent is administered locally.

10. The method of claim 1, wherein said therapeutic agent is administered systemically.

11. The method of claim 1, wherein said therapeutic agent is administered regionally.

12. The method of claim 1, wherein said therapeutic agent is administered locoregionally.

13. The method of claim 1, wherein said therapeutic agent is administered locally.

14. The method of claim 1, wherein said tumor is cancerous.

15. The method of claim 14, wherein said cancerous tumor is one or more of a brain, breast, ovarian, bladder, prostate, colon, lung, liver, pancreatic, gastric, bile duct, or uterine tumor.

16. The method of claim 1, wherein a dose of said apoptosis inducing agent is about 50 nM, which is administered over about 1 hour.

17. The method of claim 1, wherein said patient is a human.

18. The method of claim 1, wherein said apoptosis inducing agent is also said therapeutic agent but wherein said therapeutic agent is one or more of a separate dose or a slow-release form of the apoptosis inducing agent.

19. The method of claim 1, wherein said therapeutic agent and said apoptosis inducing agent comprises paclitaxel.

20. The method of claim 1, wherein said therapeutic agent comprises doxorubicin.

21. The method of claim 1, wherein said apoptosis inducing agent is formulated as one or more of microparticles or nanoparticles.

22. The method of claim 1, wherein said therapeutic agent is formulated as one or more of microparticles or nanoparticles.

23. The method of claim 1, wherein one or more of said apoptosis inducing agent or said therapeutic agent is administered with a pharmaceutically acceptable carrier.