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 (H-22) 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 (1/10/0.7wt.%), 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 H-22-implanted mice, OCP-L showed a significantly higher antitumor activity than OMI-CDDP-N or CDDP-S at a dose of 5mg/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.