Liposomes Coloaded with Paclitaxel and Doxorubicin: Analyses of Mechanical Characteristics and Synergistic Cytotoxic Action on Melanoma Cells

Abstract In this study, we report drug-induced changes in the mechanical properties of liposomal vesicles. The formulation, composed of l-α-phosphatidylcholine (SPC) and sodium deoxycholate (NaDC), was prepared using the solvent evaporation method. It was loaded separately with paclitaxel (PLX), doxorubicin (DOX), and the paclitaxel–doxorubicin (PLX–DOX) combination using the transmembrane gradient method. The effect of the incorporation of these payloads was analyzed by atomic force microscopy (AFM)-based spectroscopic experiments. Changes in the rigidity and Young’s modulus of vesicles were recorded. We observed that drug loading caused measurable alterations in the mechanical behavior of vesicles. PLX-loaded vesicles exhibited a greater Young’s modulus than those loaded with DOX. Overall, drug-induced changes in Young’s modulus could be ranked as follows: PLX ≥ PLX–DOX > DOX. Anticancer activity of the formulation was evaluated against B16–F10 melanoma cells. Using microscopy and flow cytometry, we show that PLX–DOX-loaded liposomal formulations were efficiently internalized into the cells and triggered apoptotic death through synergistic action.