Stealth liposomes for the delivery of zoledronic acid into tumors enhance the anticancer activity of the drug

Abstract

Zoledronic acid (ZOL) is a third generation aminobisphosphonate, commonly used for the treatment of bone metastases. Several studies have shown a direct in vitro antitumor activity of ZOL but a clear evidence of clinical activity is still lacking. Unfortunately, the use of ZOL as an anticancer agent in extraskeletal tissues is limited probably because it is rapidly removed from the blood and tends to accumulate in the bone. On these bases, we developed stealth liposomes encapsulating ZOL (Lipo- ZOL) to improve the pharmacokinetic profile of the drug. Compared to free ZOL, Lipo-ZOL induced a stronger inhibition of growth in two different cancer cell lines H460 and CG5. Moreover, Lipo-ZOL also significantly caused a larger inhibition of tumor growth and increased the overall survival in murine models of human lung and breast cancer, in comparison with free ZOL. These results suggest the use of Lipo-ZOL as a potential anticancer agent in patients with neoplastic disease.