Yissum - Research Development Company of the Hebrew University

Liposomal Compositions of Glucocorticoids in Anti-Cancer Therapies (LC200)

Posted by Yissum - Research Development Company of the Hebrew UniversityResponsive · Innovative Products and Technologies · Israel

Summary of the technology

chemically modified gluococorticoids (GC), in their amphipathic weak acid form enables the effective loading in liposomes of the acidic GC. Surprisingly, the thus formed liposomal weakly acidic GC was stable, i.e. the majority of the substance remained within the liposome as intact acidic GC after storage for 14 months at 4?C. Once released from the liposome to water or body fluids the acidic GC was hydrolyzed to obtain the active, non-acidic GC.
Project ID : 12-2006-1706

Description of the technology

Delivery of chemically modified gluococorticoids (GC) into the tumor site by passive loading

Categories

Drug delivery for anticancer treatments, Glucocorticoids (GCs)

Development Stage

In vivo animal studies for anticancer therapy were performed

Highlights

  • Glucocorticoids (GCs) are steroidaldrugs widely used to suppress variousallergic,inflammatory and autoimmune disorders as well as posttransplantory immunosuppressants. GCs are important components of many "cocktails" used in anti-cancer therapies.
  • A novel delivery system has been developed in order to overcome the severe side effects of GCs and non-favorable pharmacokinetic, The GCs are encapsulating in a nano delivery system that passively targets to desired tissues with favorable pharmacokinetic.

The Innovation

  • The invention involves a nano-sterically stabilized liposomes (nSSL) technology for the delivery of GCs by passive targeting into the tumor site.
  • This invention is based on the finding that chemical modification of GCs that turn them into water soluble amphipathic weak acids steroids prodrugs enables highly effective remote loading in the pegylated nano-liposomes referred to as nSSL-GC. Loading is done in a manner that enables a high drug level in each nano-liposome as well as above 90% loading efficiency and a controlled first order slow release.
  • Once released from the liposome, the acidic GC prodrug is hydrolyzed to the active GC drug.

Key Features

  • The invention take advantage on the "enhanced permeability and retention" (EPR) effect which allows passive targeting of the nSSL-GC into the tumor site releasing the drug there. This resembles the mechanism of action of Doxil™ the first liposomal and nano-drug approved by the FDA as an anticancer drug in 1996.
  • The mechanism, where the drug delivery is performed in a non-active form that turns into the active form at the target site, enhances performance.
  • nSSL-GC formulations are stable for at least 14 months when stored refrigerated (36°F to 46°F; 2°C to 8°C)

Development Milestones

  • The therapeutic effect of the GC-liposomes was demonstrated in vivo on cancer and autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS) animal models. It was shown that GC-liposomes containing methylprednisolone hemisuccinate sodium salt (MPS) have a superior effect over currently clinically available drugs in reducing the clinical signs of cancer and survival, also compared to free MPS.

The Opportunity

  • Corticosteroids are mainly used in cancer therapy to reduce swelling, mostly used with other drugs.
  • Examples for GCs used as a part of cancer therapy are Dexamethasone, Hydrocortisone, Methylprednisolone, Prednisolone and Prednisone.

Project manager

Ariela Markel
VP, Business Development, Healthcare

Project researchers

Yechezkel Barenholz
HUJI, School of Medicine - IMRIC
Biochemistry and Molecular Biology

Alberto A Gabizon
Shaare Zedek Medical Center,

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About Yissum - Research Development Company of the Hebrew University

Technology Transfer Office from Israel

Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. Founded in 1964 to protect and commercialize the Hebrew University’s intellectual property. Ranked among the top technology transfer companies, Yissum has registered over 8,900 patents covering 2,500 inventions; has licensed out 800 technologies and has spun-off 90 companies. Products that are based on Hebrew University technologies and were commercialized by Yissum generate today over $2 Billion in annual sales.

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