Targeting chemotherapy to solid tumors with long-circulating thermosensitive liposomes and local hyperthermia

The effectiveness of the combination of long-circulating, thermosensitive l iposomes and hyperthermia is described. Small-sized, thermosensitive liposo mes that encapsulate doxorubicin (DXR-PEG-TSL (SUV)) have a prolonged circu lation time and are extravasated to targeted solid tumors in vivo, where th ey preferentially release the agent in an anatomical site subjected to loca l hyperthermia, Liposomes were prepared by the incorporation of amphipathic polyethyleneglycol (PEG) to prolong their circulation time. DXR-PEG-TSL (S UV) was retained longest and was accumulated mast efficiently in solid tumo rs in Balb/c mice. The combination of DXR-PEG-TSL (SUV) and hyperthermia at the tumor sites 3 h after injection, gave high concentrations of doxorubic in in tumor tissue and resulted in more effective tumor retardation and inc reased survival time. A large amount of DXR-PEG-TSL (SUV) was extravasated into the tumors during circulation for 3 h after injection, suggesting that the encapsulated drug was released into the interstitial spaces of the les ions by local hyperthermia. This system is expected to be clinically valuab le for the delivery of a wide range of chemotherapeutic agents in the treat ment of solid tumors.