Heat-mediated selective delivery of liposomeassociated melphalan in murine melanoma

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Abstract
Malignant melanoma is notable for its resistance to chemotherapy, and multimodality approaches are being investigated to improve therapeutic efficacy. Melphalan and dacarbazine are commonly used for treatment of melanoma and their effect is potentiated by hyperthermia. The present study attempts to enhance the antitumour effect of melphalan by encapsulating it in temperature-sensitive liposomes and using it in combination with localized hyperthermic treatment of tumours for targeted delivery. Small unilamellar vesicles made of synthetic lipids (distearoyl phosphatidyl choline and dipalmitoyl phosphatidyl choline), showing gel to liquid crystalline phase transition at 42 degrees C, were used for encapsulation of melphalan. In vivo antitumour efficacy of the combination of liposomal melphalan and hyperthermia was determined using B16F10 murine melanoma transplanted into C57Bl/6 mice. A significant reduction in tumour volume and increased survival time was observed in tumour-bearing mice treated with a combination of hyperthermia and thermosensitive liposome-encapsulated melphalan compared with animals treated with an equivalent dose of free melphalan with or without hyperthermia. These results suggest that hyperthermia in combination with temperature-sensitive liposome-encapsulated melphalan may serve as a useful targeted drug delivery system for more effective management of melanoma.

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