Novel stealth self-assembled nanoparticles for the delivery of zoledronic acid in the treatment of solid tumors.

Purpose: To design and develop novel self-assembled nanoparticles (NPs) for the delivery of zoledronic acid (ZOL) in cancer therapy. Methods: NPs were prepared by two different methods. Briefly, a solution of CaCl2 and Na2HPO4 were mixed under stirring and then filtered trough 0.22 m pore filters. The resulting dispersion was mixed with an aqueous solution of ZOL (CaPZ NPs). CaPZ NPs were then incubated under stirring with PEGylated cationic liposomes at room temperature for 10 min (pre-PLCaPZ NPs). Alternatively, CaPZ NPs were mixed with cationic liposomes and the resulting particles were then incubated with micelles of PEGylated lipid at 50°C for 10 min (post-PLCaPZ NPs). The in vitro activity of PLCaPZ NPs were investigated on different cancer cell lines. Results: We prepared pre and post-PLCaPZ NPs with a mean diameters of about 147 and 309 nm and an actual loading of 65 and 15 g of ZOL/mg lipid, respectively. Morphological analysis showed that the post-PLCaP preparation consisted in an heterogeneous particle dispersion. On the contrary, spherical-shaped and homogenously dispersed NPs were found in the case of pre-PLCaPZ. In all cell lines, the NPs strengthened the growth inhibition induced by free ZOL, reaching a potentiation factor of 12 in breast carcinoma MCF7 cell line. Conclusions: New self-assembled NPs formulation for ZOL delivery has been developed in our lab. In particular, the formulation termed as pre-PLCaPZ offers the advantaged such as good technological properties and easy preparation directly before use. In addition pre-PLCaP NPs assured a strong potentiation of the ZOL toxicity in different cancer cell lines. The results obtained indicate that pre-PLCaPZ NPs could be a new and powerful tool to deliver ZOL in tumors.