Li Ming-Guang, Lu Wan-Liang, Wang Jian-Cheng, Zhang Xuan, Zhang Hua, Wang Xue-Qing, Wu Cui-Shuan, Zhang Qiang
School of Pharmaceutical Sciences, Peking University, Beijing 100083, PR China.
J Nanosci Nanotechnol. 2006 Sep-Oct;6(9-10):2874-86. doi: 10.1166/jnn.2006.411.
As most of polypeptides are marginally stable, a mild formulation procedure would be beneficial for the activities of these drugs. The objective of the present study was to develop a novel pH-sensitive nanoparticle system that was suitable for entrapment of hydrophilic insulin but without affecting its conformation. Chitosan was incorporated as a positively charged material, and one of the three poly(methylmethacrylate/methylmethacrylic acid) copolymers, consisting of Eudragit L100-55, L100, and S100, was used as a negatively charged polymer for preparation of three insulin nanoparticles, respectively. Three nanoparticles obtained were spherical. The mean diameters were in the range from 200 nm to 250 nm, and the entrapment efficiencies, from 50% to 70%. The surface analysis indicated that insulin was evenly distributed in the nanoparticles. Polymer ratio of chitosan to Eudragit was the factor which influenced the nanoparticles significantly. Characterization results showed that the electrostatic interactions existed, thus providing a mild formulation procedure which did not affect the chemical integrity and the conformation of insulin. In vitro release studies revealed that all three types of the nanoparticles exhibited a pH-dependant characteristic. The modeling data indicated that the release kinetics of insulin was nonlinear, and during the release process, the nanoparticles showed a polynomial swelling. On overall estimation, the insulin chitosan-Eudragit L100-55 nanoparticles may be better for the oral delivery. This new pH-sensitive nanoparticle formulation using chitosan and Eudragit L100-55 polymer may provide a useful approach for entrapment of hydrophilic polypeptides without affecting their conformation.
由于大多数多肽稳定性较差，温和的制剂工艺对这些药物的活性有益。本研究的目的是开发一种新型的pH敏感纳米颗粒系统，该系统适合包载亲水性胰岛素且不影响其构象。壳聚糖作为带正电荷的材料，三种聚（甲基丙烯酸甲酯/甲基丙烯酸）共聚物（包括Eudragit L100 - 55、L100和S100）之一分别用作带负电荷的聚合物来制备三种胰岛素纳米颗粒。得到的三种纳米颗粒均为球形。平均直径在200 nm至250 nm范围内，包封率在50%至70%之间。表面分析表明胰岛素在纳米颗粒中均匀分布。壳聚糖与Eudragit的聚合物比例是对纳米颗粒有显著影响的因素。表征结果表明存在静电相互作用，从而提供了一种不影响胰岛素化学完整性和构象的温和制剂工艺。体外释放研究表明，所有三种类型的纳米颗粒均表现出pH依赖性特征。模型数据表明胰岛素的释放动力学是非线性的，并且在释放过程中，纳米颗粒呈现多项式溶胀。总体评估，胰岛素壳聚糖 - Eudragit L100 - 55纳米颗粒可能更适合口服给药。这种使用壳聚糖和Eudragit L100 - 55聚合物的新型pH敏感纳米颗粒制剂可能为包载亲水性多肽且不影响其构象提供一种有用的方法。
