Objective: Metformin-loaded liposomes were optimized for enhanced antiproliferative activity against melanoma.
Methods: Box-Behnken design and response surface methodology were employed to optimize entrapment efficiency, ex-vivo permeation and vesicle size. The optimized formulation was prepared by both the lipid hydration method and the modified injection method for comparison. Different concentrations of Pluronic F127 were employed for modification. Selected Pluronic-modified formulation (lipid molar concentration 55 mmol, cholesterol 30% and drug loading 52.9 mg) was characterized for morphology, entrapment efficiency, permeation and vesicle size.
Results: The optimized formulation resulted in entrapment efficiency of 41.7 ± 0.01%, vesicle size of 1.405 ± 0.061 µm and percentage of permeation was 67 ± 5.5%. The improved cytotoxic effect of the selected formulation against melanoma mice B16 cell line compared with metformin solution was determined using MTT assay. Compared with the corresponding drug solution, the Pluronic-modified optimized liposomes displayed a highly efficient cytotoxic effect as evidenced by significant lowering in IC50 -887.3 ± 23.2 and 26.71 ± 0.69 μg/ml, respectively, P < 0.0001.
Conclusion: This study introduces an optimized liposomal formulation with enhanced cytotoxic effect against melanoma B16 cell line.
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