Localized delivery to CT-26 tumors in mice using thermosensitive liposomes

A heat-sensitive liposomal drug delivery system was tested using Colon-26 (CT-26) cultured cells and tumors in mice. Lucifer yellow iodoacetamide (LY) was used as a fluorescence marker. The heat-sensitive liposomes exploit the temperature-dependence of critical micellar concentrations of the poloxamer, F127. LY release from unilamellar liposomes at different temperatures was measured. Onset of LY release occurred near 33 degrees C, and reached plateau above 42 degrees C when 90% of the LY was released. Temperature-treated liposomes were mixed with CT-26 cells to measure the binding of the released LY to cell surface. Temperature-dependency of cell-bound LY corresponds to the release curve. CT-26 tumors were grown subcutaneously in both hind legs of Balb/c mice. Mice received heat-sensitive or plain liposomes via tail vein injections, or no liposomes. For each mouse, one tumor was kept at 31.5 degrees C, while the counterlateral tumor was heated to 42 degrees C during injection and for 30min after. LY released in tumors was determined from fluorescence intensity. Tumors receiving heat-sensitive liposomes plus heat treatment showed 2.5-fold greater fluorescence than all other tumors, which were at the background level. This study demonstrates the possible use of poloxamer-containing liposomes as a heat-sensitive drug delivery system in vivo.