In vitro and in vivo evaluation of cationic liposomes containing zoledronic acid as anticancer agent

Zoledronic acid (ZOL) is a potent amino-bisphosphonate used for the treatment of bone metastases with recently reported antitumor activity. However, its short plasma half-life as well as rapid uptake and accumulation within bone limits the use of ZOL as an antitumor agent. Cationic liposomes have a propensity for localizing in newly formed tumor vessels, improved anti-tumor efficacy associated with impaired function of the tumor microvasculature. At present study, we aim to proposed new delivery systems cationic liposomes to slow ZOL metabolize, so as to improve its effect on tumors. The antiproliferative effects of ZOL-loaded cationic liposomes (ZOL-CLPs), ZOL-loaded neutral liposomes (ZOL-NLPs), and free ZOL in the human lung adenocarcinoma A549 cell lines were evaluated by MTT assay. The advantage of ZOL-CLPs over ZOL-NLPs and free ZOL with regard to antitumor activity in vivo was evaluated in a lung tumor-bearing mouse model. The particle size, zeta potential, and entrapment efficiency (EE%) of the ZOL-CLPs were observed as 106.76 +/- 1.94 nm, +42.37 +/- 2.60 mV, and 38.54 +/- 0.99%, respectively. The antiproliferative effects experiment in vitro, the IC50 of ZOL-CLPs, ZOL-NLPs and free ZOL were 6.38 +/- 1.66, 66.92 +/- 3.75, and 184.65 +/- 12.31 mu g/mL, respectively. Compared with the control group, the tumor inhibition rate of ZOL-CLPs group, ZOL-NLPs group, free ZOL group were 48.18, 36.66, and 2.10%, respectively. Immunohistochemical study showed that the expression of VEGF protein and COX-2 protein were high in control group, medium in ZOL group, low in ZOL-NLPs group, and lower in ZOL-CLPs group. In conclusion, the ZOL-CLPs is a tumor-targeting liposomes which has significant antitumor activity against adenocarcinoma A549 cell lung cancer.