Liposomes containing zoledronic acid: a new opportunity against cancer.

Zoledronic acid (ZOL), a third-generation amino-bisphosphonate, has been approved in the US, the EU and many other countries worldwide for the prevention of skeletal-related events in patients with bone metastases of malignancy. Recently, evidence suggested that ZOL is also potent inducers of apoptosis in several cancer cell types such as myeloma and breast, prostate and pancreatic cancer as well as in macrophage and intestinal epithelial cell lines. These data indicate that the beneficial effect of ZOL on metastatic bone disease may result also from direct anti-cancer activity that may affect a broad range of tumours1. However, both the rapid elimination from plasma and the rapid uptake and accumulation within bone hamper the direct anti-cancer activity of ZOL in vivo. Liposomes have been extensively used to change drug biodistribution. In particular, liposomes with stealth properties allow to address the encapsulated drug toward tissues characterised by vessel with an enhanced permeability of the endothelium, such as tumors. In this study, a strategy to change ZOL biodistribution upon i.v. administration is proposed. In particular, we used stealth liposomes encapsulating ZOL to avoid the accumulation of the drug into the bone and increase its concentration in non-calcified tissues, e.g. in tumour tissues. ZOL-containing liposomes were prepared at different lipid composition. The in vitro activity and the cytotoxicity of ZOL-containing liposomes were investigated on different cell lines. Moreover, the selected formulation was tested in two in vivo model of multiple myeloma and prostate cancer, respectively.