title: 3-octadecylcarbamoylacrylic acid-cisplatin nanocomplexes for the development of novel liposome formulation.
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 IC50values 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 IC50compared 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.
authors.affiliation: a Department of Pharmaceutics , School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , Liaoning , P. R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Song
authors.affiliation: a Department of Pharmaceutics , School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , Liaoning , P. R. China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Xu
authors.affiliation: a Department of Pharmaceutics , School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , Liaoning , P. R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: a Department of Pharmaceutics , School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , Liaoning , P. R. China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Guo
authors.affiliation: a Department of Pharmaceutics , School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , Liaoning , P. R. China.
authors.forename: Weifang
authors.initials: W
authors.lastname: Ren
authors.affiliation: a Department of Pharmaceutics , School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , Liaoning , P. R. China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhu
authors.affiliation: a Department of Pharmaceutics , School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , Liaoning , P. R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002784:Cholesterol / Q000737:chemistry; D002945:Cisplatin / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D061986:MCF-7 Cells; D008297:Male; D051379:Mice; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D010743:Phospholipids; D002784:Cholesterol; D002945:Cisplatin
keywords: 3-octadecylcarbamoylacrylic acid; Antitumor efficacy; cisplatin; liposome; nanocomplexes