Thermochemotherapy: Synergism between hyperthermia and liposomal bleomycin in mice bearing melanoma B16F1

This study was aimed at enhancing the antitumour efficacy of bleomycin by encapsulating it in temperature-sensitive liposomes and using it in combination with localized hyperthermia of tumours for targeted delivery. Large unilammelar vesicles (LUV) made of synthetic lipids (disteroyl phosphatidylcholine and dipalmitoyl phosphatidylcholine) showing gel-to-liquid phase transition at 41°C, were used to encapsulate bleomycin. Comparison of LUV when incubated in saline at various temperatures revealed that maximum drug release (80%) occurred at 42°C compared with less than 5% release at 37°C. Better stability during storage was also observed with thermosensitive bleomycin liposomes. When administered intravenously to C57BL/6J mice bearing melanoma B16F1 tumour at 10 mg kg−1 dose, liposomal bleomycin in combination with hyperthermia (43°C, 30 min or 1 h) exhibited improved anticancer activity as evident by the enhanced volume doubling time and growth delay compared with animals treated with an equivalent dose of free bleomycin with or without hyperthermia. The results suggest that hyperthermia in combination with bleomycin encapsulated in temperature sensitive liposomes may be a useful targeted drug delivery system for more effective management of melanoma B16F1.