【摘要】 目的 制备胰岛素固体脂质纳米粒并考察其理化性质。方法 采用溶剂扩散法制备胰岛素固体脂质纳米粒,考察制备过程中加入多聚阴离子对纳米粒粒径、表面电位和药物包封率的影响;研究载药纳米粒的体外释放特性;荧光标记固体脂质纳米粒经大鼠口服给药,由荧光倒置显微镜观察血液和淋巴液中的荧光强度。结果胰岛素固体脂质纳米粒的平均粒径为(388.6±143.5)nm,水相中加入三聚磷酸钠对纳米粒粒径无明显影响,而表面电位下降,药物包封率明显增加;胰岛素固体脂质纳米粒最初1 h快速释放了药物包封总量的35.63％,随后以接近每小时1.5％的速度释放,呈明显的缓释特征,24 h体外累积释放量为药物包封量的67.30％;固体脂质纳米粒经大鼠口服研究发现,0.5 h时淋巴液中的荧光强度明显高于相同时间血液中的荧光强度。结论 采用溶剂扩散法制备得到的胰岛素固体脂质纳米粒,具有明显的药物缓释作用;通过调节纳米粒表面电位,可明显提高药物的包封率;固体脂质纳米粒口服给药,具有明显的纳米粒整体淋巴吸收特性。更多还原

【Abstract】 OBJECTIVE To prepare insulin-loaded solid lipid nanoparticles (INS-SLN) and investigate their physicochemical properties. METHODS INS-SLN was prepared by solvent diffusion method. The effects of adding polyanion into aqueous phase during preparation on the particle size, Zeta potential and drug entrapment efficiency were investigated.The drug release profile in vitro was evaluated. Fluorescein isothiocyanate (FTTC) labeled stearylamine nanoparticles were orally administered to SD rats and the fluorescent intensities of blood and lymph were evaluated by inverted fluorescent microscope. RESULTS The average size of nanoparticles prepared by solvent diffusion technique was (388.6±143.5) nm. There was no more change on particle size after tripolyphosphate sodium being added into the aqueous phase during preparation. Meanwhile, the Zeta potential of the nanosuspension was decreased and the drug entrapment efficiency was increased. After burst drug release in the first hour, a distinctly prolonged insulin release from the nanoparticles was observed in vitro and nearly 1.5 % of the drug was released per hour. About 67.30 % of insulin loaded in SLN was released in 24 hours. 0.5 h after oral administration of FTTC labeled stearylamine nanoparticles, the fluorescent intensity of the lymph photograph was obviously denser than that of blood. CONCLUSION INSSLN prepared by solvent diffusion method showed sustained release manner. The entrapment efficiency could be improved significantly through adjusting the Zeta potential of the nanoparticles. SLN may be a potential new drug carrier for enhancing the intestinal lymph absorption.更多还原