摘要
: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
OBJECTIVE To investigate the possibility of poly(ε caprolactone block D,L lactide) nanoparticles (PCLA NP) as a new kind of drug carrier.METHOD INS PCLA NP was prepared by double emulsification solvent evaporation method. Its morphology was examined by transmission electron microscope. HPLC method was established for INS in INS PCLA NP, the encapsulation ratio of INS on INS PCLA NP was estimated, and the influence factors to size and encapsulation ratio were investigated. The in vitro INS release behaviour from nanoparticles was determined. An “antibody capture” procedure was devised for testing encapsulation mechanism. The diabetic rats model was established and to evaluate the hypoglycemic effects after subcutaneous administration of INS PCLA NP. The pharmacological bioavailability (PBA) was calculated from the area above the curve (AAC).RESULTS The mean diameter of INS PCLA NP was 167.3 nm, while the encapsulation ratio of INS reached to 37.79%. It was demonstrated that the most (about 53%) encapsulated INS was on the surface of the nanoparticles, it could be measured by “antibody capture” experiment. INS release from INS PCLA NP appeared to consist of two components with an initial rapid release followed by a slower exponential stage. After subcutaneous administration of INS PCLA NP 12u·kg -1 , the hypoglycemic effect was significant. The pharmacological bioavailability of INS PCLA NP was 74.76%.CONCLUSION PCLA NP might be a potential new drug carrier.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2001年第1期38-42,共5页
Chinese Pharmaceutical Journal
基金
国家自然科学基金资助项目! (5 983314 0 )
