Sun Shaoping, Liang Na, Gong Xianfeng, An Weiwei, Kawashima Yoshiaki, Cui Fude, Yan Pengfei
Key Laboratory of Chemical Engineering Process and Technology for High-Efficiency Conversion, School of Chemistry and Material Science, College of Heilongjiang Province (Heilongjiang University), Heilongjiang University, Harbin 150080, China.
College of Chemistry and Chemical Engineering, Harbin Normal University, Harbin 150025, China.
Int J Mol Sci. 2016 Dec 28;18(1):54. doi: 10.3390/ijms18010054.
In this study, we designed and developed a new drug delivery system of multifunctional composite microcapsules for oral administration of insulin. Firstly, in order to enhance the encapsulation efficiency, insulin was complexed with functional sodium deoxycholate to form insulin-sodium deoxycholate complex using hydrophobic ion pairing method. Then the complex was encapsulated into poly(lactide--glycolide) (PLGA) nanoparticles by emulsion solvent diffusion method. The PLGA nanoparticles have a mean size of 168 nm and a zeta potential of -29.2 mV. The encapsulation efficiency was increased to 94.2% for the complex. In order to deliver insulin to specific gastrointestinal regions and reduce the burst release of insulin from PLGA nanoparticles, hence enhancing the bioavailability of insulin, enteric targeting multifunctional composite microcapsules were further prepared by encapsulating PLGA nanoparticles into pH-sensitive hydroxypropyl methyl cellulose phthalate (HP55) using organic spray-drying method. A pH-dependent insulin release profile was observed for this drug delivery system in vitro. All these strategies help to enhance the encapsulation efficiency, control the drug release, and protect insulin from degradation. In diabetic fasted rats, administration of the composite microcapsules produced a great enhancement in the relative bioavailability, which illustrated that this formulation was an effective candidate for oral insulin delivery.
在本研究中，我们设计并开发了一种用于口服胰岛素的多功能复合微胶囊新型给药系统。首先，为提高包封率，采用疏水离子对法将胰岛素与功能性脱氧胆酸钠络合形成胰岛素-脱氧胆酸钠复合物。然后通过乳液溶剂扩散法将该复合物包封于聚（丙交酯-乙交酯）（PLGA）纳米粒中。PLGA纳米粒的平均粒径为168 nm，ζ电位为-29.2 mV。该复合物的包封率提高到了94.2%。为了将胰岛素递送至特定的胃肠道区域并减少胰岛素从PLGA纳米粒中的突释，从而提高胰岛素的生物利用度，采用有机喷雾干燥法将PLGA纳米粒包封于pH敏感型羟丙基甲基纤维素邻苯二甲酸酯（HP55）中，进一步制备了肠靶向多功能复合微胶囊。在体外观察到该给药系统呈现pH依赖性的胰岛素释放曲线。所有这些策略有助于提高包封率、控制药物释放并保护胰岛素不被降解。在糖尿病禁食大鼠中，给予复合微胶囊后相对生物利用度有显著提高，这表明该制剂是口服胰岛素递送的有效候选物。
