Jintapattanakit Anchalee, Junyaprasert Varaporn B, Mao Shirui, Sitterberg Johannes, Bakowsky Udo, Kissel Thomas
Department of Pharmacy, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayutthaya, Bangkok 10400, Thailand.
Int J Pharm. 2007 Sep 5;342(1-2):240-9. doi: 10.1016/j.ijpharm.2007.05.015. Epub 2007 May 17.
Polymeric delivery systems based on nanoparticles (NP) have emerged as a promising approach for peroral insulin delivery. Using a trimethyl chitosan (TMC) and a PEG-graft-TMC copolymer, polyelectrolyte complexes (PEC) and nanoparticles were prepared and their properties were compared. The amount of insulin was quantified by HPLC and the stability of PEC and NP upon exposure to simulated gastrointestinal (GI) fluid was monitored by dynamic laser light scattering. It was shown that polymer/insulin (+/-) charge ratio played an important role in PEC and NP formation. Stable, uniform, and spherical PEC/NP with high insulin association efficiency (AE) were formed at or close to optimized polymer/insulin (+/-) charge ratio, depending on polymer structure. All PEC were more stable in pH 6.8 simulated intestinal fluid (SIF) than NP. The PEC also appeared to play some role in protecting insulin from degradation at higher temperature and with proteolytic enzyme more efficiently than NP. On the basis of these results, polyelectrolyte complexation can be suggested as a potentially useful technique for generating insulin delivery systems for peroral administration.
基于纳米颗粒（NP）的聚合物递送系统已成为口服胰岛素递送的一种有前景的方法。使用三甲基壳聚糖（TMC）和聚乙二醇接枝三甲基壳聚糖（PEG-graft-TMC）共聚物制备了聚电解质复合物（PEC）和纳米颗粒，并对它们的性质进行了比较。通过高效液相色谱法（HPLC）对胰岛素的含量进行定量，并通过动态激光散射监测PEC和NP在模拟胃肠道（GI）液中的稳定性。结果表明，聚合物/胰岛素（+/-）电荷比在PEC和NP的形成中起重要作用。根据聚合物结构，在或接近优化的聚合物/胰岛素（+/-）电荷比时，形成了具有高胰岛素结合效率（AE）的稳定、均匀且呈球形的PEC/NP。所有PEC在pH 6.8的模拟肠液（SIF）中比NP更稳定。与NP相比，PEC在较高温度下和存在蛋白水解酶时，似乎在保护胰岛素不被降解方面也发挥了一定作用。基于这些结果，聚电解质络合可被认为是一种潜在有用的技术，用于生成口服给药的胰岛素递送系统。
