Preparation and effect of bone targeting drug of the epirubicin-oxidized dextran-alendronate compound for osteosarcoma cells / 中国医师杂志

ABSTRACT

Objective To prepare a new bone-targeted drug of epirubicin-oxidized dextran-alendronate compound,and explore the effect of compound on osteosarcoma cells.Methods (1) Based on Schiff's base theory,we synthesized the compound.(2) We investigated physicochemical character with ultraviolet (UV),infrared (IR),and 1H-nuclear magnetic resonance (1H-NMR),molecular weight and aldehyde group content in oxidized dextran,alendronate content in oxidized dextran-alendronate compound,epirubicin drug loading capacity in the compound,and rate of charge for three matters,and affinity to bone in vitro though Hydroxyapatite (HA) absorbing test.(3) We investigated the compound's cytotoxicity effect through methyl thiazolyl tetrazolium (MTT) test,apoptosis influence through flow cytometry (FCM).Results (1) There were typical physicochemical characters.(2) Oxidized dextran molecular weight (MW) was 4 251 ± 68,number of average molecular weight (MN) was 2 551 ± 42,and molecular weight distribution width was 1.78.Aldehyde group content of oxidized dextran was (10.41 ± 0.2)mmol/mg,epirubicin drug loading capacity was (5.28 ± 0.23) ％,rate of charge was 5,and 2 ～ 3 between aldehyde group content in oxidized dextran and alendronate (ALN).(3) In the MTT test,epirubicin (EPI)-Dex-ALN,EPI,ALN obviously restrained osteosarcoma cell proliferation,the minimum concentration(μg/ml) was 1,1,and 40; IC50 (μg/ml) of EPI-Dex-ALN,EPI,ALN was 0.142,0.505,0.219; 0.251,0.739,and 0.518; 45.21,27.97,and 18.96 after 24 h,48 h,72 h; in FCM (flow cytometry),apoptosis and necrosis rate of EPI-Dex-ALN,ALN,and Dex was 80.13 ±4.05,97.01 ±2.58,31.53 ±6.9,and 14.01 ±2.51.Conclusions We successfully synthesized a new bone-targeted drug delivery system,which showed better bone affinity in vivo,and kept biological activity with powerful targeted function.