Targeted liposomes

Abstract

The present invention is in the field of drug delivery, and specifically, cationic liposome-based drug delivery. In embodiments, this invention provides methods of making ligand-targeted (e.g., antibody- or antibody fragment-targeted) liposomes useful for the delivery of liposomes to tumors, including brain tumors. In embodiments, the liposomes deliver temozolomide across the blood-brain barrier for treatment of primary or metastatic brain tumors. Additional cancers that can be treated with the liposomes include neuroendocrine tumors, melanoma, prostate, head and neck, ovarian, lung, liver, kidney, breast, urogenital, gastric, colorectal, cervical, vaginal, angiosarcoma, liposarcoma, rhabdomyosarcoma, choriocarcinoma, pancreatic, retinoblastoma and other types of cancer. In another embodiment the liposomes deliver melphalan for the treatment of multiple myeloma, other tumors of the blood or other solid tumors. In still other embodiments the liposomes can deliver other drugs such as pemetrexed or irinotecan for treatment of cancer or drugs including atropine for treatment of organophosphate poisoning.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]The present application claims the benefit of U.S. Provisional Patent Application Nos. 61 / 702,796, filed Sep. 19, 2012, and 61 / 767,453, filed Feb. 21, 2013, the disclosures of each of which are incorporated by reference herein in their entireties.BACKGROUND OF THE INVENTION[0002]1. Field of the Invention[0003]The present invention is in the field of drug delivery, and specifically, cationic liposome-based drug delivery. In embodiments, this invention provides methods of making ligand-targeted (e.g., antibody- or antibody fragment-targeted) liposomes useful for the delivery of liposomes to tumors, including brain tumors. In embodiments, the liposomes deliver temozolomide across the blood-brain barrier for treatment of primary or metastatic brain tumors. Additional cancers that can be treated with the liposomes include, but are not limited to, neuroendocrine tumors, melanoma, prostate, head and neck, ovarian, lung, liver, breast, kidney, ur...

AI Technical Summary

Benefits of technology

The patent text describes methods for preparing targeted liposome complexes of temozolomide and melphalan using cationic lipids. The methods involve preparing a lipid solution by mixing cationic lipids with a solution of temozolomide or melphalan in a ratio of lipid to drug of about 1:1. The lipid solution is then injected into an aqueous solution to form the liposome complex. The resulting liposome complex can be further modified by adding a ligand, such as an anti-transferrin receptor single chain Fv (TfRscFv) to create a targeted liposome complex. The methods provide a simple and effective way to prepare targeted liposome complexes for the treatment of glioblastoma, melanoma, and other cancer types.

Problems solved by technology

Primary brain tumors, and particularly gliomas, are one of the most difficult cancers to treat.

The lack of improvement in the prognosis of patients with brain cancer over the last few years, despite recent advances in drug discovery and development of targeted therapies, is due in large part to the inability of the therapeutics to cross the blood-brain barrier (BBB) (Blakeley, J.

Biochemical and Biophysical Research Communications 406: pp 311-314), however myelosuppression, neutropenia and thrombocytopenia are among its side effects and therapeutic dosages are limited by these.

The extensive tissue distribution that results from the non-tumor specific uptake of the orally administered TMZ is a major cause of these side effects.

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