马利敏, 张强, 李玉珍, 顾忠伟. 胰岛素聚酯微粒的制备及大鼠体内药效学研究J. 药学学报, 2000, 35(11): 850-853.
引用本文: 马利敏, 张强, 李玉珍, 顾忠伟. 胰岛素聚酯微粒的制备及大鼠体内药效学研究J. 药学学报, 2000, 35(11): 850-853.
MA Li-min, LI Yu-zheng, ZHANG Qiang, GU Zhong-wei. STUDY ON PREPARATION AND PHARMACODYNAMICS OF INSULIN-LOADED POLYESTER MICROPARTICLESJ. Acta Pharmaceutica Sinica, 2000, 35(11): 850-853.
Citation: MA Li-min, LI Yu-zheng, ZHANG Qiang, GU Zhong-wei. STUDY ON PREPARATION AND PHARMACODYNAMICS OF INSULIN-LOADED POLYESTER MICROPARTICLESJ. Acta Pharmaceutica Sinica, 2000, 35(11): 850-853.

胰岛素聚酯微粒的制备及大鼠体内药效学研究

STUDY ON PREPARATION AND PHARMACODYNAMICS OF INSULIN-LOADED POLYESTER MICROPARTICLES

  • 摘要: 目的 探讨利用一种新型聚酯材料—ε-己内酯-D,L-丙交酯嵌段共聚物(PCLA)制备微粒型药物载体的可能性。方法 通过双乳化溶剂蒸发技术制备ε-己内酯-D,L-丙交酯嵌段共聚物微粒(PCLA-MP),用扫描电镜观察其形态,粒径分析仪(particle analyser)测定粒径;以胰岛素(INS)为模型药物,制备胰岛素聚酯微粒(INS-PCLA-MP);建立了测定INS包封率的HPLC方法;INS抗体捕捉实验考察PCLA-MP载药机理;以pH 7.4的磷酸盐缓冲液为介质,探讨INS-PCLA-MP体外释药特性;建立了药物致大鼠糖尿病模型,通过葡萄糖氧化酶法(GOD-PAP)测定血糖值来评价INS-PCLA-MP经皮下给药后的降血糖作用;以INS-SOL为对照,计算药理相对生物利用度。结果 制备的微粒大小均匀,表面光滑圆整,平均粒径1.9 μm;INS的包封率为76.46%;抗体捕捉实验证实,被包封的INS中只有小部分(18.25%)分布在MP的表面;INS-PCLA-MP的体外释放曲线包括突释相及随后的缓慢释放相;药效学研究表明,12 u.kg-1的INS-PCLA-MP经糖尿病大鼠皮下给药后具有明显的降血糖作用,药理相对生物利用度为132.95%。结论 PCLA嵌段共聚物作为药物输送系统的载体材料有着良好的前景,PCLA-MP有可能成为一种新型的药物载体。

     

    Abstract: AIM To investigate the possibility of using poly (ε-caprolactone-block-D,L-lactide) (PLCA) as a kind of materials to prepare the microparticles drug carrier. METHODS PCLA-MP (microparticle, MP) was prepared by double-emulsification solvent evaporation method. Its morphology was examined by scanning electron microscope. Its size diameter was examined by particle analyser. Insulin (INS), as a model drug, was then encapsulated into PCLA-MP (INS-PCLA-MP). HPLC method was established for determining INS in INS-PCLA-MP. An “antibody-capture” procedure was devised for investigating encapsulation mechanism. The in vitro release behaviour of INS-PCLA-MP was determined in phosphatic buffer solution (pH 7.4). The diabetic rat model was established and blood glucose levels were measured using glucose oxidase (GOD-PAP) method to evaluate the hypoglycaemic effects after subcutaneous administration of INS-PCLA-MP. The pharmacological bioavailability (PBA) of INS-PCLA-MP was calculated from the area above the curve (AAC) in contrast with INS-solution. RESULTS The mean diameter of INS-PCLA-MP was 1.9 μm, while the encapsulation ratio of INS reached to 76.46%. Only 18.25% encapsulated INS was on the surface of the microparticles, it could be measured by “antibody-capture” experiment. The in vitro release curve of INS-PCLA-MP consists of initial rapid release stage followed by slower exponential stage. In pharmacodynamic studies, after subcutaneous administration of INS-PCLA-MP 12 u.kg-1, the hypoglycaemic effect was significant. The PBA of INS-PCLA-MP was 123.08%. CONCLUSION PCLA might become a new drug carrier material in the future.

     

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