Ma L M, Zhang Q, Li Y Z, Gu Z W
Department of Pharmacy, People's Hospital of Beijing Medical University, Beijing 100044, China.
Yao Xue Xue Bao. 2000 Nov;35(11):850-3.
To investigate the possibility of using poly (epsilon-caprolactone-block-D, L-lactide) (PLCA) as a kind of materials to prepare the microparticles drug carrier.
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.
The mean diameter of INS-PCLA-MP was 1.9 microns, 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%.
PCLA might become a new drug carrier material in the future.
研究使用聚（ε-己内酯-嵌段-D，L-丙交酯）（PLCA）作为一种材料制备微粒药物载体的可能性。
采用复乳溶剂蒸发法制备PLCA微粒（MP）。通过扫描电子显微镜观察其形态。用颗粒分析仪检测其粒径。然后将胰岛素（INS）作为模型药物包封到PLCA-MP中（INS-PCLA-MP）。建立HPLC法测定INS-PCLA-MP中的INS。设计了一种“抗体捕获”程序来研究包封机制。在磷酸盐缓冲溶液（pH 7.4）中测定INS-PCLA-MP的体外释放行为。建立糖尿病大鼠模型，用葡萄糖氧化酶（GOD-PAP）法测量血糖水平，以评估皮下注射INS-PCLA-MP后的降血糖效果。与INS溶液相比，根据曲线下面积（AAC）计算INS-PCLA-MP的药理生物利用度（PBA）。
INS-PCLA-MP的平均直径为1.9微米，而INS的包封率达到76.46%。通过“抗体捕获”实验可测得，仅18.25%的包封INS位于微粒表面。INS-PCLA-MP的体外释放曲线包括初始快速释放阶段，随后是较慢的指数阶段。在药效学研究中，皮下注射12 u.kg-1的INS-PCLA-MP后，降血糖效果显著。INS-PCLA-MP的PBA为123.08%。
PLCA未来可能成为一种新型药物载体材料。
