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

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.