LTSL (lysolipid thermally sensitive liposome) technology provides an elegant solution to the challenge of effective chemotherapy. LTSL is engineered with a unique liposomal technology that delivers locally high concentrations of drug—up to 25 times the systemic dose—in a region targeted with the application of tolerable heat.
“Leaky” tumor blood vessels promote access of liposomes
There is general agreement in the medical community that tumor blood vessels are abnormal, with “leaky” endothelium being the primary manifestation. Blood vessel leakiness influences, among other things, access of therapeutic agents to tumor cells. 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 application further increases liposomal penetration
An external heating device gently heats the tumor tissue to greater than 40°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-sensitive liposomes selectively release chemotherapeutic agent
Heat application also produces important changes in the liposome. When tissue reaches a tolerable 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 surrounding vasculature. This method damages only the tumor and the area related to tumor invasion.
These 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, LTSL enables delivery of higher concentrations of proven chemotherapy drugs directly to the tumor, stopping the progression of cancer and minimizing systemic toxicity.
LTSL technology is agnostic regarding the means of heating. Whether combined with radiofrequency thermal ablation (RFA) to expand the “treatment zone” for solid tumors, microwave ablation for superficial tumors, or high-intensity focused ultrasound for difficult to reach tumors, LTSL has shown its mechanism to be effective.
While ThermoDox®, liposomal encapsulation of doxorubicin, is our first investigational product developed through application of LTSL technology, the LTSL platform has shown its applicability to a variety of drug products including formulations of docetaxel and carboplatin. Celsion licensed the exclusive worldwide rights to the LTSL technology from Duke University.
Products using LTSL: ThermoDox
ThermoDox uses our LTSL technology to encapsulate doxorubicin, a proven and commonly used cancer drug.
ThermoDox is currently being evaluated a phase 3 study for treatment of primary liver cancer and in a phase 2 study for recurrent chest wall breast cancer.
