LTLD: Effective, elegant, patented

Our approach is based on Lyso-Thermosenstive Liposomal Doxorubicin (LTLD), a unique liposomal technology with a novel mechanism of action that delivers high concentrations of drug in a region targeted with the application of localized heat.

“Leaky” Tumor Blood Vessels – There is general agreement in the medical community that tumor blood vessels are abnormal. The primary manifestation of this abnormality is a defective, or “leaky”, endothelium. Blood vessel leakiness influences a number of factors within the tumor, including the access of therapeutic agents to tumor cells. Even at normal body temperature (37°C), the blood vessels that supply blood to tumors are leakier than those found in healthy tissue. Administered as a standard intravenous infusion, Celsion’s specially designed liposomes circulate through the bloodstream and into the tumor through the leaky tumor vasculature, concentrating at the tumor site.

Heat Adds Permeability – An external heating device gently heats the tumor tissue to approximately 42°C. The localized administration of heat accentuates the leakiness by increasing the porosity of the tumor vasculature, causing more drug-delivering liposomes to be carried into the tumor.

Heat-Triggered, Mechanical Release – When tissue reaches a temperature of 40°C or greater, the heat-sensitive liposome rapidly changes structure and the liposomal membrane selectively dissolves, creating openings that release the chemotherapeutic agent directly into the tumor and into the surrounding vasculature, but only where the heat is present. This method damages only the tumor and the area related to tumor invasion.

These new liposomes are composed of lipid molecules that quickly change structure when heated to a specific temperature, creating channels in the liposome bilayer that allow encapsulated drug to rapidly disperse into the surrounding tissue. As a result, LTLD enables delivery of higher concentrations of proven chemotherapy drugs directly to the tumor, stopping the progression of cancer and minimizing systemic toxicity.

LTLD technology, when combined with radiofrequency thermal ablation (RFA), can expand the “treatment zone” for primary liver cancer, while addressing the limitations of RFA. By itself, RFA does not target micro-metastases outside the so-called “ablation zone.” ThermoDox®, the first product developed through application of LTLD technology, is a heat-activated liposomal encapsulation of the chemotherapy drug doxorubicin. In the treatment of primary liver cancer, ThermoDox is infused 15 minutes prior to RFA administration. Ablation then releases doxorubicin in the “thermal zone,” where the drug concentrates while expanding the treatment area outward to the ablation zone.

The LTLD platform has the ability to be applied to a variety of drug products. In addition to ThermoDox, Celsion is applying its LTLD technology platform to develop liposomal formulations of docetaxel and carboplatin.

Celsion licensed the exclusive worldwide rights to the LTLD technology from Duke University.