Can stealth liposomes convert a bisphophonate in a anticancer agent?

Purpose: To develop long circulating liposomes encapsulating ZOL in order to avoid the accumulation of the drug into the bone and increase its concentration in non-calcified tissues, e.g. in tumour tissues. Methods: The liposomes encapsulating ZOL (lipoZ) were prepared by a modified reverse-phase evaporation technique followed by extrusion. The resulting liposomes were then purified and freeze-dried in presence of a cryoprotectant. In vitro and in vivo activity of lipoZ, were investigated in different cancer cell lines and in mice models of prostate cancer and a multiple myeloma, respectively. Results: We prepared lipoZ at different lipid composition with a mean size ranged between 203 and 241 nm and an actual loading from about 77 to 101 g ZOL/mg lipids. The formulation with the higher ZOL retention after freeze-drying/rehydration was selected for further studies on cells and in vivo. In all cell lines, lipoZ strengthened growth inhibition induced by free ZOL. In vivo studies, in both mice cancer models, lipoZ induced a strong tumour growth inhibition with an increased mice overall survival. This effect was significantly higher than that observed with free ZOL. Conclusion: In this study, both anti-cancer activity and tolerability of ZOL-containing liposomes were demonstrated in preclinical animal models. When encapsulated into liposome, ZOL showed a powerful anticancer effect, while the tumors were resistant to free ZOL used at the same doses.