Zhang Huan, Wang Weimei, Li Haoran, Peng Yi, Zhang Zhiqing
a The Second Hospital of Hebei Medical University , Shijiazhuang , Hebei , PR China.
b Harrison International Peace Hospital , Hengshui , Hebei , PR China.
Drug Dev Ind Pharm. 2018 Jan;44(1):109-115. doi: 10.1080/03639045.2017.1386197. Epub 2017 Oct 17.
Insulin-loaded microspheres were prepared by alternating deposition film layers that were composed of insulin and poly(vinyl sulfate) potassium on the surface of poly(lactic acid) (PLA) microspheres. The preparation of the insulin-loaded microspheres was optimized by an orthogonal test design, and the relationship between drug loading (DL) and film layers was studied. The particle size, DL and encapsulation efficiency of the obtained insulin-loaded microspheres with 10 films were 5.25 ± 0.15 µm, 111.33 ± 1.15 mg/g and 33.7 ± 0.19%, respectively. Following this, the physical characteristics of the insulin-loaded microspheres were investigated. The results from scanning electron microscopy and a laser particle size analyzer (LPSA) indicated the spherical morphology, rough surface and increasing particle sizes of the insulin-loaded microspheres, which were compared to those of PLA microspheres. An in vitro release study showed that the insulin-loaded microspheres were stable in HCl solution (pH 1.0) and released insulin slowly in phosphate-buffered solution (pH 6.8). Finally, the drug efficacy of the prepared insulin-loaded microspheres via oral administration was evaluated in rats with diabetes induced by streptozotocin, and an obvious dose-dependent hypoglycemic effect was observed. This preliminary data could illustrate the prospect of using microspheres for the oral delivery of insulin.
通过在聚乳酸（PLA）微球表面交替沉积由胰岛素和聚（硫酸乙烯酯）钾组成的薄膜层来制备载胰岛素微球。采用正交试验设计对载胰岛素微球的制备工艺进行优化，并研究载药量（DL）与薄膜层数之间的关系。所制备的具有10层薄膜的载胰岛素微球的粒径、载药量和包封率分别为5.25±0.15μm、111.33±1.15mg/g和33.7±0.19%。随后，对载胰岛素微球的物理特性进行了研究。扫描电子显微镜和激光粒度分析仪（LPSA）的结果表明，与PLA微球相比，载胰岛素微球具有球形形态、粗糙表面且粒径增大。体外释放研究表明，载胰岛素微球在盐酸溶液（pH 1.0）中稳定，在磷酸盐缓冲溶液（pH 6.8）中缓慢释放胰岛素。最后，在链脲佐菌素诱导的糖尿病大鼠中评估了所制备的载胰岛素微球经口服给药后的药效，观察到明显的剂量依赖性降血糖作用。这些初步数据可以说明使用微球进行胰岛素口服递送的前景。
