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 RESEARCH PAPER
Year : 2000  |  Volume : 32  |  Issue : 3  |  Page : 214-220

Thermosensitive liposomes and localised hyperthermia - an effective bimodality approach for tumour management



Correspondence Address:
Sandip B Tiwari


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Source of Support: None, Conflict of Interest: None


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Objectives: To entrap methotrexate (MTX) in thermosensitive liposomes, to characterise liposomes for different physicochemical properties and to investigate the potential of liposome entrapped MTX and localised hyperthermia (HT) in management of melanoma B16F1. Methods: Thermosensitive liposomes, made of synthetic lipids (distearoylphosphatidylcholine, DSPC and dipalmitoyl phosphatidyl choline, DPPC) showing gel to liquid phase transition at 41o C, were used for encapsulation of methotrexate. The liposomes were prepared by reverse phase evaporation method. The entrapment efficiency of the drug within the liposomes was determined by gel filtration on Sephadex G-50 column. The in vitro release studies of the vesicles were conducted by incubating the drug encapsulated liposomes in saline at various temperatures for 15 min. The vesicle stability was assessed by storage at room temperature, 37o C and under refrigeration (4o C) for a period of three months. The MTX containing liposomes were administered intravenously to C57BL/6J mice bearing melanoma B16F1 tumour at 12 mg kg-1 dose. Immediately after the drug administration, localised hyperthermia treatment was applied by placing the tumours in water bath at 43o C either for 30 min. or 1 hr. The volume doubling time and growth delay of the tumour were taken as parameters to assess the antitumour efficacy. Results: The thermosensitive liposomes encapsulated about 52% of the MTX. Comparison of the drug release profile at various temperatures revealed that maximum drug release (83%) occurred at 42o C compared to less than 5% release at 37o C. Better stability on storage was also observed with thermosensitive MTX liposomes. The thermosensitive liposomes and localised hyperthermia produced an improved anticancer activity as evident by enhanced volume doubling time and growth delay. Conclusion: These results suggest that localised hyperthermia in combination with temperature sensitive liposome encapsulated MTX may serve as a useful targeted drug delivery system for more effective management of melanoma B16F1.






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