Delivery of therapeutic compounds via microparticles or microbubbles

• US 20040126400A1
• Filed: 09/22/2003
• Published: 07/01/2004
• Est. Priority Date: 05/03/2002
• Status: Abandoned Application

• Current Assignee: Avi Biopharma, Inc.
• Original Assignee: Avi Biopharma, Inc.
• Inventors: Iversen, Patrick L., Kipshidze, Nicholas
• Application Number:
  US10/668,988
• Publication Number:
  US 20040126400A1
• Time in Patent Office: Days
• US Class Current: 424/400
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61K 47/6925 the form being a microcapsule, nanocapsule, microbubble or nanobubble
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/167 with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface with further drug-free outer coating A61K9/5073
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors

Abstract

Microparticle carriers, particularly protein-encapsulated microbubbles, are used to deliver antiproliferative drugs to target sites in a subject. In particular, antirestenotic drugs are delivered to areas of vascular injury for treatment or prevention of hyperproliferative disease, e.g. stenosis, in blood vessels; and antineoplastic drugs are targeted to tumor sites.

Claims

5. The composition of claim 5, wherein the agent is selected from the group consisting of rapamycin, paclitaxel, and docetaxel.

9. A method for delivering an antiproliferative therapeutic agent to the site of a tumor in a subject, comprising:

administering parenterally to a subject having said tumor a composition comprising said agent and a suspension of microbubbles which are encapsulated with a filmogenic protein and contain a gas selected from a perfluorocarbon and SF₆.

1. A composition comprising (i) a suspension of microbubbles which are encapsulated with a filmogenic protein and contain a gas selected from a perfluorocarbon and SF₆, and (ii) a non-antisense antiproliferative therapeutic agent.

2. The composition of claim 1, wherein the gas is a perfluorocarbon selected from the group consisting of perfluoromethane, perfluoroethane, perfluoropropane, perfluorobutane, and perfluoropentane.

3. The composition of claim 1, wherein the protein is human serum albumin.

4. The composition of claim 1, wherein the agent is selected from the group consisting of rapamycin, paclitaxel, docetaxel, tacrolimus, and active analogs, derivatives or prodrugs of these compounds.

6. The composition of claim 1, wherein the agent is selected from the group consisting of cisplatin, carboplatin, etoposide, tamoxifen, methotrexate, 5-fluorouracil, adriamycin, daunorubicin, doxorubicin, amsacrine, mitotane, topotecan, tretinoin, hydroxyurea, procarbazine, carmustine, mechlorethamine hydrochloride, cyclophosphamide, ifosfamide, chlorambucil, melphalan, busulfan, thiotepa, carmustine, estramustine, dacarbazine, omustine, streptozocin, vincristine, vinblastine, vinorelbine, vindesine, fludarabine, fluorodeoxyuridine, cytosine arabinoside, cytarabine, azidothymidine, cysteine arabinoside, azacytidine, mercaptopurine, thioguanine, cladribine, pentostatin, arabinosyl adenine, dactinomycin, daunorubicin, doxorubicin, amsacrine, idarubicin, mitoxantrone, bleomycin, plicamycin, ansamitomycin, mitomycin, aminoglutethimide, and flutamide.

7. The composition of claim 6, wherein the agent is selected from the group consisting of cisplatin, carboplatin, etoposide, tamoxifen, methotrexate, 5-fluorouracil, adriamycin, daunorubicin, doxorubicin, vincristine, and vinblastine.

8. The composition of claim 1, wherein said composition is formed by incubating said agent with said suspension of microbubbles.

10. The method of claim 9, wherein said administration is carried out without application of external stimulation to said composition during or following administration.

11. The method of claim 9, wherein the gas is a perfluorocarbon selected from the group consisting of perfluoromethane, perfluoroethane, perfluoropropane, perfluorobutane, and perfluoropentane.

12. The method of claim 9, wherein the protein is human serum albumin.

13. The method of claim 9, wherein the agent is selected from the group consisting of rapamycin, paclitaxel, docetaxel, tacrolimus, and active analogs, derivatives or prodrugs of these compounds.

14. The method of claim 13, wherein the agent is selected from the group consisting of rapamycin, paclitaxel, and docetaxel.

15. The method of claim 9, wherein the agent is selected from the group consisting of cisplatin, carboplatin, etoposide, tamoxifen, methotrexate, 5-fluorouracil, adriamycin, daunorubicin, doxorubicin, amsacrine, mitotane, topotecan, tretinoin, hydroxyurea, procarbazine, carmustine, mechlorethamine hydrochloride, cyclophosphamide, ifosfamide, chlorambucil, melphalan, busulfan, thiotepa, carmustine, estramustine, dacarbazine, omustine, streptozocin, vincristine, vinblastine, vinorelbine, vindesine, fludarabine, fluorodeoxyuridine, cytosine arabinoside, cytarabine, azidothymidine, cysteine arabinoside, azacytidine, mercaptopurine, thioguanine, cladribine, pentostatin, arabinosyl adenine, dactinomycin, daunorubicin, doxorubicin, amsacrine, idarubicin, mitoxantrone, bleomycin, plicamycin, ansamitomycin, mitomycin, aminoglutethimide, and flutamide.

16. The method of claim 9, wherein the agent is a non-antisense agent.

17. The method of claim 9, wherein said composition is formed by incubating said agent with said suspension of microbubbles.

15-1. The method of claim 14, wherein the antiproliferative agent is selected from the group consisting of cisplatin, carboplatin, etoposide, tamoxifen, methotrexate, 5-fluorouracil, adriamycin, daunorubicin, doxorubicin, vincristine, and vinblastine.