摘要
为了提高胰岛素的口服生物利用度,本研究以聚乙二醇聚乳酸共聚物(PEG-PLA)为高分子载体材料、磷脂s75为脂质材料、Eudragit L100为肠溶材料制备口服胰岛素肠溶聚合物脂质杂化纳米粒(INS-NPs L100),并对其体内外性能进行评价。采用W/O/W复乳溶剂挥发法制备胰岛素聚合物脂质杂化纳米粒(INS-NPs),以包封率、粒径和释药行为为评价指标,采用单因素法对处方进行优化;将最优INS-NPs与肠溶材料Eudragit^■L100混合制备成INS-NPs L100,并对其形态、体外释放及健康大鼠灌胃后的降血糖作用进行评价。以最优处方制备的INS-NPs包封率为(62.18±4.51)%,平均粒径为(225.2±94.3)nm,多分散系数为0.191±0.068,Zeta电位为-(14.84±1.26)mV。包裹肠溶材料后所制备的INS-NPs L100,在pH1.0盐酸溶液中2h累积释放量为8.01%,在pH6.8的磷酸盐缓冲液中6h累积释放量为67.31%。将所制备的INS-NPs L100经口给予健康大鼠(38IU/kg)后,具有明显的持续降血糖作用,3.5h时血糖浓度可降至初始值的76%。实验结果表明,本研究所制备的INS-NPsL100可有效减缓胰岛素在胃液中的释放速度,提高蛋白在胃肠道中的稳定性,为多肽、蛋白类药物口服给药提供了新的研究思路。
To improve the oral bioavailability of insulin,an insulin-loaded enteric polymer-lipid hybrid nanoparticles (INS-NPs L100) was prepared using methoxy PEG-poly(D,L-lactide)(PEG-PLA),phospholipid s75 and Eudragit L100;in vitro and in vivo behaviors of INS-NPs L100 were evaluated.Insulin-loaded polymer-lipid hybrid nanoparticles (INS-NPs) were prepared by W/O/W double emulsion solvent evaporation method.INS-NPs formulation was optimized by single factor experiment using encapsulation efficiency,particle size,and in vitro release behavior of the corresponding INS-NPs L100 as evaluation indexes.The morphology, in vitro drug release profile and hypoglycemic effect of the INS-NPs L100 using the optimal INS-NPs and Eudragit^■L100 (used as enteric polymer) were assessed.The results showed that the encapsulation efficiency of the optimal INS-NPs was (62.18±4.51)%.The average particle size,PDI and Zeta potential was (225.2±94.3) nm,0.191±0.068,and -(14.84±1.26) mV,respectively.The cumulative drug release from the INS-NPs L100 was only 8.01% at 2 h in pH 1.0 HCl solution,exhibiting a slow drug release behavior;while the drug release from INS-NPs L100 was 67.31% at 6 h in phosphate buffer of pH 6.8.Mereorer,after oral administration of INS-NPs L100 with a dose of 38 IU/kg,the blood glucose concentration of healthy rats was reduced to 76% of the initial values at 3.5 h , exhibiting a sustained hypoglycemic effect.In summary,the INS-NPs L100 prepared in this study could effectively decrease the release rate of insulin in gastric juice,improve the stability of protein in the gastrointestinal tract,and provide a new approach for the oral administration of peptides and protein drugs.
作者
林霞
李娜
李金蔚
杨子毅
金坚
LIN Xia;LI Na;LI Jinwei;YANG Ziyi;JIN Jian(School of Pharmaceutical Sciences,Jiangnan University,Wuxi 214122,China)
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2019年第3期308-316,共9页
Journal of China Pharmaceutical University
基金
国家自然科学基金资助项目(No.81603060)
江苏高校品牌专业建设工程资助项目(No.PPZY2015B146)~~
