Treatment of experimental bladder cancer with hyperthermia and phase transition liposomes containing methotrexate

Serially transplanted murine bladder cancer was treated with localized capacitive radiofrequency hyperthermia and liposome-delivered methotrexate (MTX). Liposomes were manufactured to retain MTX at 37C but specifically release encapsulated MTX as they passed through preheated tumors. When compared to controls, neither free MTX nor liposome-delivered MTX caused significant tumoricidal activity. Heat alone did cause a slowing of tumor growth and an increase in animal survival. Because large unilamellar liposomes are known to be cleared by the liver, sixteen animals were autopsied to determine the extent of liver toxicity which may have been a result of the various treatments. No hepatotoxic effects were observed after injection of liposomes containing MTX or other experimental combinations of drug and/or liposomes.