摘要
目的 合成表阿霉素-氧化葡聚糖-阿仑膦酸钠聚合物,探讨其骨靶向特征.方法 根据席夫碱原理,合成氧化葡聚糖-阿仑膦酸钠聚合物、表阿霉素-氧化葡聚糖-阿仑膦酸钠聚合物;通过红外、紫外光谱和核磁共振波谱氢谱对聚合物进行表征.体外羟基磷灰石结合实验验证聚合物的体外亲骨性,荧光显微技术验证其体内亲骨性,液相色谱仪观察聚合物在小鼠各脏器和不同时间段的组织分布.结果 红外、紫外光谱和核磁共振波谱氢谱证明氧化葡聚糖、氧化葡聚糖-阿仑膦酸钠聚合物、表阿霉素-氧化葡聚糖-阿仑膦酸钠聚合物合成成功.体外羟基磷灰石吸附实验显示表阿霉素-氧化葡聚糖-阿仑膦酸钠聚合物和表阿霉素的吸附率分别为86.13％和13.91％.体内亲骨性实验显示荧光主要为骨干骺端的皮质骨和松质骨,骨髓中无明显发现,表阿霉素-氧化葡聚糖-阿仑膦酸钠聚合物的荧光强度约为表阿霉素的2.7倍.选择注射表阿霉素和表阿霉素-氧化葡聚糖-阿仑膦酸钠聚合物后10 min、1、2、24和48 h对各脏器药物浓度进行测定,发现注射2h后达到最大组织浓度,表阿霉素和表阿霉素-氧化葡聚糖-阿仑膦酸钠聚合物在器官分布中存在差异,而骨组织中的药物浓度在给药后10 min、1、2和24 h差异有统计学意义,48 h差异无统计学意义.结论 成功合成的骨靶向药物具有良好的体内、体外亲骨性,具有明显的骨靶向特征.
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 system：epirubicin-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.
出处
《中华骨科杂志》
CAS
CSCD
北大核心
2014年第9期945-953,共9页
Chinese Journal of Orthopaedics
基金
武汉大学研究生资助科研项目（201130302020006）
