左氧氟沙星羧甲基壳聚糖微球结肠靶向释药的实验研究

目的:检测所制备的左氧氟沙星羧甲基壳聚糖(LVFX/CMC)微球在人工消化液中和大鼠体内结肠靶向释药的性能。方法:以分光光度仪测定微球在人工消化液中的累积释放量,电镜观察微球在人工消化液中形态的改变。SD大鼠60只,随机分为两组,分别以LVFX/CMC微球(含40 mg左氧氟沙星)及等量左氧氟沙星溶剂灌胃,以高效液相色谱法对LVFX/CMC微球和左氧氟沙星(LVFX)灌胃后大鼠盲肠、结肠中药物浓度进行定量检测。结果:左氧氟沙星壳聚糖微球在人工胃液介质中溶解缓慢,2 h仅释药8.62%;在人工小肠液介质中溶解速度稍见加快,6 h释药29.39%,但表现为药物缓释曲线,24 h仅释药42.13%;在人工结肠液中,4 h后释药84.56%,24 h内累积释药量为93%。扫描电镜观察人工胃液中的微球明显溶胀,稍见变形;人工结肠液中的微球溶解,粒径明显减小。灌胃后LVFX/CMC微球组5和9 h时段盲肠、结肠药量明显高于LVFX组。结论:左氧氟沙星羧甲基壳聚糖微球在体外、体内实验中的释放符合结肠靶向释药的特点。

Study on colon-specific delivery of carboxymethylchitosan microspheres containing levofloxacin

Objective:To evaluate the colon-specific delivery of levofloxacin-carboxymethylchitosan microspheres(LVFX/CMC)in artificial medium and in rats.Methods:Microspheres were achieved by emulsification and cross-linking process.The in vitro release of microspheres in artificial alimentary juice was carried out with spectrophotometer and scanning electron microscopy.Sixty healthy male SD rats were divided randomly into 2 groups.One group received LVFX solution(40 mg,control group)and the other were treated with LVFX/CMC microspheres(40 mg,treatment group) by gastric lavage.HPLC was used to detect the concentrations of LVFX in the cecum and colon in both groups.Results:The accumulative release of LVFX/CMC microspheres was 8.62% in the artificial gastric juice for 2 h and 29.39% in the artificial small intestinal juice for 6 h,while the release reached to about 84.56% for LVFX/CMC microspheres in the artificial colon liquid for 4 h,and 93% for 24 h.The significant degradation of the LVFX/CMC microspheres was observed in the artificial colon liquid by SEM.At five and nine hours after administration,the levels of LVFX in cecum and colon were obviously higher in treatment group than those in control group.Conclusions:LVFX/CMC microspheres showed the potential of colon targeting property to release the levofloxacin in vitro and in rats.