Preparation and bone targeting effect of the epirubicin-oxidized dextran-alendronate compound / 中华骨科杂志

ABSTRACT

Objective To prepare a new bone-targeting drug of epirubicin-oxidized dextran-alendronate compound,and investigate the compound's bone targeting effect.Methods Based on Schiff base theory,we synthesized a new bone-targeted drug delivery systemepirubicin-oxidized dextran-alendronate compound.The physicochemical character was evaluated through ultra-violet (UV) spectroscopy,infrared (IR) spectroscopy and nuclear magnetic resonance (1H-NMR) spectroscopy.The character of affinity to bone in vitro was evaluated through HA absorbing test and the affinity to bone in vivo was evaluated by fluorescence microscopy.Drug distribution in different organs and different time point were investigated through liquid chromatograph.Results There were typical physicochemical characters of dextran,oxidized dextran,Dex-ALN compound,EPI-Dex-ALN compound through UV spectroscopy,IR spectroscopy and 1H-NMR spectroscopy,showed successful preparation of the bone targeting drug.HA binding rates were 86.13％,13.91％ in epirubicin-oxidized dextran-alendronate compound and epirubicin groups respectively through HA absorbing test in vitro.Luminescence microscope showed luminescence located in cortical bone,cancellous bone of metaphysic,no luminescence was found in bone marrow in affinity to bone in vivo.Compared by EPI group,IOD value of fluorescence in EPI-Dex-ALN group was 2.7 times.In HPLC drug concentration test,we detected drug concentration in different organs during the period of 10 min,1 h,2 h,24 h,48 h after injection in EPI,EPI-Dex-ALN compound group.The maximum concentration was at 2 h,and tissue distribute was different in different organs; there was statistical difference during the period of 10 min,1 h,2 h,24h,no statistical difference during the period of 48 h after injection in bone tissue between EPI group and EPI-Dex-ALN compound group.Conclusion We successfully synthesized a new bone-targeting drug delivery system,which showed better bone affinity in vivo and in vitro,and had powerful targeting function.