摘要
目的 探索可生物降解乳酸 羟基乙酸共聚物 [poly(lactic co glycolicacid) ,PLGA]纳米粒作为大分子蛋白质类口服给药系统的可能性。方法 用复乳溶剂挥发法制备了胰岛素乳酸 羟基乙酸共聚物纳米粒 (INS PLGA NPs) ;光子相关光谱法测定了平均粒径 ;HPLC法测定了胰岛素的包封率 ;放射免疫法研究了纳米粒的载药方式 ;考察了INS PLGA NPs的体外释放特性 ;评价了口服给予纳米粒对糖尿病大鼠降血糖作用。结果 以 1%poloxamer 188为乳化剂制备的纳米粒 ,平均粒径为 14 9 6nm ,多分散度为 0 0 9,包封率为 4 2 8% ;同时抗体捕捉实验发现纳米粒主要以吸附方式载药 ;胰岛素的体外释放分为两相 ;以 10u·kg- 1 的剂量给予该纳米粒 ,4h后血糖浓度显著降低 (P <0 0 5 ) ,10h血糖降至最低 ,药理相对生物利用度 (10 3± 0 8) %。结论 PLGA NPs可能成为大分子蛋白质药物口服给药的新型载体。
AIM To investigate the possibility of poly(lactic co glycolic acid) as a carrier f or the delivery of macromolecular. METHODS Insulin loaded poly(lactic co glycolic acid) nanoparticles (INS PLGA NPs) w as prepared by a double emulsion solvent evaporation method. Th e size distribution was examined by photo correlation spectrometry. The entrapm ent efficiency was determined by HPLC and important factors that affected the en trapment efficiency were investigated. The loading mechanism of different size n anoparticles was assayed by radioimmunoassay (RIA). INS PLGA NPs release behav ior in vitro was carried out under sink condition. After oral administration of the nanoparticles to alloxan induced diabetic rats, its glucose level was d etermined by glucose oxidize method and the oral pharmacological bioavailability in contrast to sc of insulin solution was calculated according to the area over the curve. RESULTS The INS PLGA NPs was prepared with poloxamer 188 as a emulsifier, the mean dia meter was 149 6 nm and the polydispersity index was decreased to 0 09. While t he entrapment efficiency was increased to 42 8%. Most of the insulin loaded was adsorbed on the surface of the nanoparticles. The release behavior in vitro showed an initial burst effect followed by a slower rate stage. After oral admi nistration of 10 u·kg -1 INS PLGA NPs, the plasma glucose level decr eased significantly after 4 h ( P <0 05 ), 10 h later the glucose level de creased to the lowest (52 4%±10 2%, P <0 01 ) and the relative pharmac ological bioavailability is (10 3±0 8)%. CONCLUSION PLGA NPs might be used as a new oral carrier for protein drug delivery systems in the future.
出处
《药学学报》
CAS
CSCD
北大核心
2002年第5期374-377,共4页
Acta Pharmaceutica Sinica
