多西他赛人血白蛋白微球的制备及体外释药性质的评价

发布时间：2018-01-21 07:06

本文关键词： 多西他赛人血白蛋白微球正交设计　出处：《中国医院药学杂志》2017年12期 　论文类型：期刊论文

【摘要】：目的:通过优选工艺条件制备多西他赛人血白蛋白微球,并考察其体外缓释特性。方法:以人血白蛋白为药物载体,采用乳化-化学交联法制备多西他赛蛋白微球,HPLC测定多西他赛的浓度,通过L16(45)正交设计试验考察药质比、交联剂用量、交联时间、搅拌转速、酸碱度等因素对微球载药量和包封率的影响,利用极差分析和方差分析优选最佳工艺条件;扫描电镜观察微球形态;以累积释药百分率为指标考察微球体外释药特性。结果:最佳工艺条件为药质比为1∶7、交联剂用量为2.0mL、交联时间为1.5h、搅拌转速为300r·min-1、反应介质pH值为7.5;以优化工艺制备的微球在扫描电镜下可见为表面光滑的类球体,平均粒径为36.16μm,载药量为(11.74±0.26)%,包封率为(65.24±1.24)%,体外释药模式符合Higuchi方程Q=14.34t1/2+0.21(r=0.994 5),48h体外累积释药百分率为82.8%。结论:本实验通过优化工艺条件,制备完成载药量、包封率和缓释性均较为理想的多西他赛人血蛋白微球。
[Abstract]:Objective: to prepare docetaxel human albumin microspheres and investigate their sustained release characteristics in vitro. Methods: human serum albumin was used as drug carrier. Docetaxel microspheres were prepared by emulsification-chemical crosslinking method. The concentration of docetaxel was determined by HPLC. The drug mass ratio, the amount of crosslinking agent and the crosslinking time were investigated by orthogonal design. The effects of stirring speed, pH and pH on the drug loading and encapsulation efficiency of microspheres were studied. The optimum technological conditions were selected by means of range analysis and variance analysis. The morphology of microspheres was observed by scanning electron microscope. The results showed that the optimum conditions were as follows: the ratio of drug to substance was 1: 7, the dosage of crosslinking agent was 2.0 mL, and the crosslinking time was 1.5 h. The stirring speed is 300r 路min-1, the pH value of the reaction medium is 7.5; The microspheres prepared by the optimized technology can be seen as smooth spheres with an average diameter of 36.16 渭 m and a drug load of 11.74 卤0.26% under scanning electron microscope. The entrapment efficiency was 65.24 卤1.24, and the drug release model in vitro was in accordance with the Higuchi equation QT 14.34 t ~ (1 / 20) 0.21% ~ 0.994 5). Conclusion: through the optimization of the technological conditions, the complete drug loading, encapsulation efficiency and sustained release of docetaxel hemoglobin microspheres were satisfactory.
【作者单位】：南方医科大学皮肤病医院(广东省皮肤病医院);中山大学肿瘤防治中心;广东食品药品职业学院;
【基金】：广东省医学科学基金(编号:B2013071、B2016083)
【分类号】：R943
【正文快照】： 多西他赛(docetaxel,DT)是广谱高效的抗癌药,可促进微管蛋白二聚体装配成微管,并抑制其解聚,从而阻碍癌细胞的有丝分裂[1-2],发挥抗癌作用。多西他赛溶解性较差,使用时须以聚山梨酯-80及乙醇作为溶媒进行配制,然而静脉注射聚山梨酯-80极易引起溶血、过敏、神经毒性等不良反应[

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