Author/Authors :
Malaekeh- Nikouei, Bizhan Nanotechnology Research Center - Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad , Gholami, Leila Department of Modern Sciences and Technologies - School of Medicine - Mashhad University of Medical Sciences, Mashhad , Kazemi Oskuee, Reza Targeted Drug Delivery Research Center, Mashhad University of Medical Sciences, Mashhad , Mohammadi, Ali Department of Drug and Food Control - School of Pharmacy, Tehran University of Medical Science, Tehran, , Amanolahi, Farjad Department of Drug and Food Control - School of Pharmacy, Tehran University of Medical Science, Tehran
Abstract :
Objective (s): This study aimed at investigating the preparation and stability 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-loaded 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 :
Curcumin , Combination therapy , Cytotoxicity , Liposome , Mitomycin