3-octadecylcarbamoylacrylic acid-cisplatin nanocomplexes for the development of novel liposome formulation.

It was the first time that 3-octadecylcarbamoylacrylicacid-cisplatin nanocomplexes (OMI-CDDP-N) were synthesized via monocarboxylato and O→Pt coordination. The nanocomplexes exhibited lower IC50 values compared with cisplatin (CDDP) in vitro, and enhanced antitumor efficacy in murine liver cancer (H22) in vivo. However, the toxicity of the nanocomplexes was more severe than CDDP. OMI-CDDP-N-based liposome (OCP-L) was prepared in order to maintain the efficacy and reduce the toxicity of OMI-CDDP-N. Here, a series of parameters were investigated to optimize liposome formulation. The optimal formulation was CDDP/phospholipids/cholesterol (1/10/0.7 wt.%), with distilled water as hydration medium and an encapsulation efficiency of 94.2 ± 2.1%. In vitro cytotoxicity studies revealed that OCP-L and OMI-CDDP-N exhibited a lower IC50 compared with commercial cisplatin injection (CDDP-S) in a variety of human cancer cells. In H22-implanted mice, OCP-L showed a significantly higher antitumor activity than OMI-CDDP-N or CDDP-S at a dose of 5 mg/kg (p < 0.01). Moreover, OCP-L exceeded the size cutoff for kidney clearance, hence it bypassed the nephrotoxicity of CDDP which is a major curse of CDDP in the clinic. These results suggested that the unique OMI-CDDP-N-entrapped liposome can overcome the disadvantages associated with conventional CDDP therapy and provide a higher safety profile.