Curcumin improved liposomal mitomycin-induced cell toxicity in bladder cancer cell

Objective (s): This study aimed at investigation of preparation and stability study of Mitomycin and Mitomycin loaded nanoliposems and efficacy of the combination of Mitomycin -loaded nanoliposomes and Curcumin versus Mitomycin in suppressing HTB-9 and L929 cell lines, in vitro.Materials and Methods: An HPLC method was validated based on Q2 (R1) International Conference on Harmonization (ICH) guideline for determination of Mitomycin in pharmaceutical samples. Soybean phosphatidylcholine (SPC) or hydrogenated soybean phosphatidylcholine (HSPC) mixed with cholesterol at 2:1 molar ratio respectively in two different groups to prepare Mitomycin nanoliposomes. Cell toxicity of free Mitomycin, Mitomycin loaded liposomes and curcumin was measured using MTT assay in bladder cancer cell line for treatment group and Fibroblast-like cell as control group. Also, propidium iodide staining was done to determine the level of DNA fragmentation.Results: The validated HPLC method showed stability based on the ICH guideline (n=3 and RSD<2%). Encapsulation efficiency values were 78 and 63 % for SPC and HSPC liposomes, respectively. Sizes of SPC and HSPC liposomes were 112 and 128 nm, respectively. Encapsulation efficiency of Mitomycin was 27 and 21 % for SPC and HSPC liposomes, respectively. Addition of Curcumin to the samples remarkably improved Mitomycin cytotoxicity. Concerning DNA fragmentation, Curcumin exhibited a protective effect when used in combination with Mitomycin.Conclusion: Synergistic effects of Curcumin and Mitomycin were observed in terms of cell toxicity. Together, since Curcumin exerts anti-oxidative properties, its co-administration with a chemotherapeutic agent might protect normal cells from adverse effects of such drugs.

Keywords:

Mitomycin , Curcumin , Liposome , Combination therapy , Cytotoxicity