Stealth liposomes and new self-assembly nanoparticles for the delivery of zoledronic acid: a comparative study.

Purpose. To propose two different strategies for the delivery of zoledronic acid (ZOL) into solid tumors. In particular, we designed and developed long circulating liposomes (LipoZOL) and self-assembly PEGylated nanoparticles (NPs) containing ZOL. Materials and methods. We prepared LipoZOL at different lipid composition by a modified reverse-phase evaporation technique, followed by extrusion, purification and lyophilization. Alternatively, self-assembling PEGylated nanoparticles, obtained by mixing an aqueous solution of ZOL with calcium phosphates nanoparticles (CaPZ NPs) and cationic liposomes, were developed. The two different nanocarriers were compared in terms of technological characteristics and the anti-cancer activity in a xenograft model of prostate adenocarcinoma. Results. We obtained LipoZOL and PLCaPZ NPs with a mean diameters of about 270 and 147 nm, respectively. PLCaPZ NPs was characterized by a narrower size distribution, as showed by the polidispesity index lower than 0.2 versus 0.4 obtained with LipoZOL. The actual loading of LipoZOL and PLCaPZ NPs was about of 108 and 66 ???g/mg lipids, respectively. The encapsulation efficiency, in the case of PLCaPZ NPs, was of about 66%, while this value dramatically dropped (< 6%) when encapsulating ZOL into LipoZOL. Finally, in human prostate cancer xenografts, the treatment of mice with LipoZOL and PLCaPZ NPs elicited a marked antitumor activity, achieving a tumor weight inhibition an about 45% and 65%, respectively. These effects are not observed in animals treated with free ZOL. Conclusion. Both developed formulations elicited a significant antitumor activity in an experimental model of prostate cancer. However, the formulation here named as PLCaPZ NPs compared to LipoZOL, offers the best technological characteristics and the possibility to prepare NPs before the use should overcome issues for long-term storage.