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:目的 探讨ε 己内酯 D ,L 丙交酯嵌段共聚物纳米粒 (PCLA NP)作为新型药物载体的可能性。方法 采用双乳化溶媒蒸发法制备了胰岛素嵌段共聚物纳米粒 (INS PCLA NP) ,透射电镜考察其形态 ;HPLC测定胰岛素的包封率 ,并考察了影响纳米粒粒径及包封率的各种因素 ;应用抗体捕捉实验验证纳米粒的载药机制 ;考察INS PCLA NP的体外释药特性 ;建立了糖尿病大鼠模型 ,通过葡萄糖氧化酶法 (GOD PAP)测定血糖浓度来评价INS PCLA NP经皮注后的降血糖作用 ,并计算INS PCLA NP的药理生物利用度 (pharmacologicalbioavailability ,PBA)。结果 INS PCLA NP的平均粒径为 16 7.3nm ;纳米粒的平均包封率为 37.79 % ;PVA浓度和超声时间对粒径及包封率影响显著 ;抗体捕捉实验证实被包封的胰岛素大部分 (约 5 3 % )存在于纳米粒的表面 ;INS PCLA NP的体外释药曲线分为两相 :突释释药相和缓释平台相 ;药效学研究表明 ,12u·kg-1的INS PCLA NP经皮下给药后即有明显的降血糖作用 ,药理生物利用度为 74.76 %。结论 PCLA NP将可能成为一种新型的药物载体
: Objective To investigate the possibility of using ε-caprolactone D, L-lactide block copolymer nanoparticles (PCLA NP) as a novel drug carrier. Methods Insulin block copolymer nanoparticles (INS PCLA NP) were prepared by double-emulsion solvent evaporation method. The morphology of insulin-loaded block copolymer nanoparticles was investigated by transmission electron microscopy. The encapsulation efficiency of insulin was measured by HPLC. The mechanism of drug-loading of nanoparticles was validated by antibody capture experiments. The in vitro release characteristics of INS-PCLA NPs were investigated. A rat model of diabetes was established. The blood glucose levels of glucose-oxidase (GOD PAP) Hypoglycemic effect after skin injection, and calculate the pharmacological bioavailability (PBA) of INS PCLA NP. Results The average particle size of INS PCLA NP was 16 7.3 nm. The average entrapment efficiency of nanoparticles was 37.79%. The concentration of PVA and ultrasonic time significantly affected the particle size and entrapment efficiency. The antibody capture experiments showed that most of the encapsulated insulin (About 53%) was present on the surface of the nanoparticles. The in vitro release curve of INS PCLA NP was divided into two phases: the burst release phase and the slow release platform phase. The pharmacodynamic studies showed that INS PCLA NP had obvious hypoglycemic effect after subcutaneous administration, the pharmacological bioavailability was 74.76%. Conclusion PCLA NP may become a new type of drug carrier