Yissum Research Development Company of the Hebrew University of Jerusalem Ltd.

Alza Corporation

Lipomedix Pharmaceuticals Ltd.

Shaare Zedek Scientific Ltd

Hadassah Medical Organization

Other

The University of North Carolina at Chapel Hill

Linear Technology Corporation

King's College London

Hadasit Medical Research, Inc.

Yissum Research and Development Company Et Al.

Sharre Zedek Scientific Ltd.

Alberto Gabizon

Yechezkel Barenholz

Samuel Zalipsky

Hilary Shmeeda

Patricia Ohana

Theresa M Allen

John Maher

Andrew Zhuang Wang

Eliezer Kedar

Yuval Avnir

Ana Catarina Parente Pereira

A liposome composition comprising a lipophilic prodrug of mitomycin C having an improved pharmacokinetic profile is described. A method for preparing the composition with a solvent system comprised of ethanol and tertiary butanol mixed at an adequate ratio is also described. In an embodiment, the liposome composition is a population of lipid nanoparticles and a pharmaceutically acceptable vehicle, wherein the population of lipid nanoparticles is comprised of a first fraction of spherical liposomes and a second fraction of rod-shaped lipid nanoparticles, where the second fraction is less than about 15% of the population of lipid nanoparticles.

Liposome composition comprising liposomal prodrug of mitomycin c and method of manufacture

A composition comprising liposomes comprising a lipid layer defining an internal aqueous compartment, an anthracycline drug entrapped in the internal aqueous phase and mitomycin C prodrug incorporated into the lipid layer is described.

Liposome composition co-encapsulating doxorubicin and a prodrug of mitomycin C

The present disclosure provides liposomes comprising a membrane and an intraliposomal aqueous water phase, the membrane comprising at least one liposome forming lipid and the intraliposomal aqueous water phase comprises a salt of a bisphosphonate together with an amphipathic weak base agent (PLAD). An example of a liposome is one comprising co encapsulated in the intraliposomal aqueous water phase N-containing bisphosphonate, such as alendronate, and an anthracycline such as doxorubicin which was shown to increase survival as compared to Doxil or to administrations of liposomal alendronate (PLA) and Doxil (separate liposomes). Such liposomes may carry a targeting moiety exposed at the liposome's outer surface, for example, conjugate of folic acid as a targeting moiety to folate receptor (FT-PLAD). Also provided by the present disclosure is a method of preparing the liposomes and methods of use of the liposomes, at times, in combination with additional active ingredients, such as &#x3b3;&#x3b4; T-cells.

Liposomes co-encapsulating a bisphosphonate and an amphipathic agent

The present invention is based on a finding of an unexpected synergistic and safe combination of antineoplastic agents which when administered in combination provides greater efficacy than the single agents alone. Accordingly, a method of treating neoplasia in a subject in need of treatment is provided, by administering to the subject an amount of a prodrug of mitomycin C that yields a therapeutically effective amount of mitomycin C, in combination with an amount of a chemotherapeutic agent. In one embodiment, the prodrug of mitomycin C is a liposomal-prodrug of mitomycin C. Together, the prodrug of mitomycin C and chemotherapeutic agent provide a synergistic antineoplastic effect.

Combination chemotherapy comprising a liposomal prodrug of mitomycin C

A method of treating neoplasia in a subject in need of treatment is provided by administering to the subject an amount of a prodrug of mitomycin C that yields a therapeutically effective amount of mitomycin C, in combination with radiation therapy. In one embodiment, the prodrug of mitomycin C is a liposomal-prodrug of mitomycin C. Together, the prodrug of mitomycin C and radiation therapy provide a synergistic antineoplastic effect.

Combination therapy comprising a liposomal prodrug of mitomycin C and radiotherapy

The present invention provides pharmaceutical compositions comprising a glucocorticoid or glucocorticoid derivative stably encapsulated in a liposome. The glucocorticoid or glucocorticoid derivative is selected from an amphipathic weak base glucocorticoid or glucocorticoid derivative having a pKa equal or below 11 and a logD at pH 7 in the range between &#x2212;2.5 and 1.5; or an amphipathic weak acid GC or GC derivative having a pKa above 3.5 and a logD at pH 7 in the range between &#x2212;2.5 and 1.5. The therapeutic effect of the pharmaceutical composition of the invention was exhibited in vivo with appropriate models of multiple sclerosis and cancer.

Liposomal compositions of glucocorticoid and glucocorticoid derivatives

Methods for administering mitomycin C to a multi-drug resistant cell and for reducing the toxicity of the compound are described. In the methods, mitoymic C is provided in the form of a prodrug conjugate, where the drug is linked to a hydrophobic moiety, such as a lipid, through a cleavable dithiobenzyl linkage. The dithiobenzyl linkage is susceptible to cleavage by mild thiolysis, resulting in release of mitomycin C in its original form. The linkage is stable under nonreducing conditions. The prodrug conjugate can be incorporated into liposomes for administration in vivo and release of mitomycin C in response to endogenous in vivo reducing conditions or in response to administration of an exogenous reducing agent.

Method for treating multi-drug resistant tumors

Conjugates of a hydrophobic moiety, such as a lipid, linked through a cleavable dithiobenzyl linkage to a therapeutic agent are described. The dithiobenzyl linkage is susceptible to cleavage by mild thiolysis, resulting in release of the therapeutic agent in its original form. The linkage is stable under nonreducing conditions. The conjugate can be incorporated into liposomes for administration in vivo and release of the therapeutic agent in response to endogeneous in vivo reducing conditions or in response to administration of an exogeneous reducing agent.

Conjugate having a cleavable linkage for use in a liposome

A method of antitumor therapy is described in which administration of a chemotherapeutic drug, encapsulated in liposomes, is supplemented by administration of an immunostimulating cytokine. The cytokine is preferably also encapsulated in liposomes. In tumor models for lung and colon carcinomas, this method produced a significantly greater therapeutic effect, as evidenced by survival rate and tumor size, than a combination of the effects produced by the free or liposome-encapsulated components administered individually.

Combined chemo-immunotherapy with liposomal drugs and cytokines

A drug/liposome composition comprising an aqueous suspension of liposomes and, entrapped in the lipid bilayer region of the liposomes, an anthraquinone drug containing quinone and hydroquinone functionalities on adjacent anthracene rings. An iron-specific trihydroxamic chelating agent contained in the bulk aqueous phase of the suspension and a lipophilic free-radical scavenger contained in the bilayer region of the liposome cooperate to reduce chemical modification of both drug and lipid components of the composition. A preferred composition containing doxorubicin and alpha-tocopherol entrapped in the liposomes, and ferrioxamine in the aqueous suspension phase is effective in treating human neoplasms, with significantly reduced side effects over those produced by free-drug administration.

Liposome/anthraquinone drug composition and method

A composition of liposomes which contain an entrapped pharmaceutical agent and are characterized by (a) liposome sizes predominantly between about 0.07 and 0.5 microns; (b) at least about 50 mole percent of a membrane-rigidifying lipid, such as sphingomyelin or neutral phospholipids with predominantly saturated acyl chains; and (c) between about 5-20 mole percent of a glycolipid selected from the group consisting of ganglioside GM.sub.1, saturated phosphatidylinositol, and monogalactosyl stearate. The liposomes show high blood/RES tissue distribution ratios, and are effective for drug administration to tumors via intravenous drug delivery.

Growing community of inventors

Jerusalem, Israel

Alberto Gabizon