3-octadecylcarbamoylacrylic acid-cisplatin nanocomplexes for the development of novel liposome formulation. (21st November 2016)

• Record Type: Journal Article
• Authors: Song, Juan; Xu, Tingting; Zhang, Yi; Guo, Hongyu; Ren, Weifang; Zhu, Shanshan; Yang, Li
• Is Part Of: Drug delivery. Volume 23:Number 9(2016:Dec.)
• Page Start: 3285
• Page End: 3293
• Publication Date: 2016-11-21
• Subjects: Antitumor efficacy -- cisplatin -- liposome -- nanocomplexes -- 3-octadecylcarbamoylacrylic acid; Drug delivery systems -- Periodicals; Drug targeting -- Periodicals; 615.05
• DOI: 10.3109/10717544.2016.1172369
• Languages: English
• ISSNs: 1071-7544

Abstract

Abstract: 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.