胰岛素肠溶PLGA纳米粒的制备及体内外性质的评价

目的制备肠溶胰岛素PLGA纳米粒,并对其理化性质、体外释药以及在正常大鼠体内的降血糖效果进行研究。方法采用改良的乳化溶剂扩散法分别制备了胰岛素PLGA纳米粒和肠溶胰岛素纳米粒(PLGA HP55 NP、PLGA HP50 NP)。通过激光粒度测定仪测定粒径大小,系统考察了肠溶材料HP55的用量及类型对纳米粒性质的影响,以及各种纳米粒在人工胃液、人工肠液中的释药行为和其在正常大鼠体内的降血糖作用,并与PLGA HP50 NP进行了比较。结果制得的最终处方的肠溶纳米粒(PLGA HP55)的粒径为(169±16)nm,胰岛素的载药量为(3.17±0.24)%。肠溶纳米粒在人工胃液中的释药速率明显低于PLGA纳米粒。PLGA纳米粒和肠溶PLGA HP50、PLGA HP55纳米粒均能显著降低正常大鼠的血糖浓度,其在正常大鼠体内24 h相对于皮下注射给药的相对生物利用度分别为(5.46±0.7)%、(6.31±0.64)%和(8.72±0.5)%。结论胰岛素肠溶纳米粒可以有效抑制胰岛素在人工胃液中的释放,与PLGA纳米粒相比显著降低正常大鼠的血糖浓度。其中PLGA HP55纳米粒的降糖作用显著高于PLGA HP50纳米粒。pH值高的纳米粒有望成为胰岛素口服给药的有效载体。

Preparation and characterization of insulin loaded PLGA-HP55 nanoparticles

Objective To prepare insulin loaded enteric PLGA nanoparticles and characterize the physicochemical properties,in vitro release behavior and hypoglycemic effects in normal rats.Methods The PLGA nanoparticles and enteric PLGA nanoparticles(PLGA-HP55 NP and PLGA-HP50 NP)were prepared by a modified emulsion solvent diffusion method in water.The average particle size of the nanoparticles was measured in a laser particle analyzer.The release behavior in SGF/SIF and the effects of enteric polymers on the properties of the nanoparticles were studied.The hypoglycemic effects in normal rats were investigated.Results The particle sizes and the drug content of the final nanoparticles were(169±16)nm and(3.17±0.24)%,respectively.The release of insulin from PLGA-HP55 nanoparticles and PLGA-HP50 nanoparticles in SGF was markedly reduced compared with PLGA nanoparticles.All nanoparticles could decrease the serum glucose levels in normal rats effectively.The relative bioavailability of PLGA,PLGA-HP50 and PLGA-HP55 nanoparticles was(5.46±0.7)%,(6.31±0.64)% and(8.72±0.5)%,respectively.Conclusions Insulin loaded enteric nanoparticles can reduce the release of insulin in SGF and enhance the hypoglycemic effect in normal rats.PLGA-HP55 nanoparticles show more predominant hypoglycemic effect than PLGA-HP50 nanoparticles,implying that the PLGA-HP55 nanoparticles could be a useful carrier for the oral administration of insulin.