Abstract
Zoledronic acid, a new highly potent third generation aminobisphosphonate, is the drug currently used to prevent bone resorption in patients with bone metastases. Moreover, ZOL is a potent inducer of apoptosis in several cancer cell types, suggesting a direct anti-cancer activity that may affect a broad range of tumors. However, the rapid elimination from plasma, along with the rapid uptake and accumulation within bone, hampers the direct anti-cancer activity of ZOL in vivo. On the other hand, long circulating nanocarriers offer the opportunity to change the pharmacokinetics of encapsulated drugs, targeting tissues with an increased permeability of the vessels (e.g. tumors). In this study, we proposed two different strategies in order to avoid ZOL accumulation in bone and address the drug toward tumors. In particular, we designed and developed long circulating liposomes and self-assembly PEGylated nanoparticles for the delivery of ZOL into solid tumors.
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