Laboratory of Pharmaceutical Technology and Biopharmaceutics, University of Bonn, Bonn, Germany.
Int J Pharm. 2013 Feb 25;443(1-2):169-74. doi: 10.1016/j.ijpharm.2013.01.017. Epub 2013 Jan 14.
Nanoparticles (NPs) have shown a certain potential to overcome the drawbacks of oral peptide delivery in the gastrointestinal tract such as low peptide stability and permeability. The preparation of insulin loaded NPs was carried out with Eudragit RL or RS dissolved in different non-toxic polyethylene glycol (PEG) derivatives. The use of these non-toxic solvents allowed the design of an one step NP preparation method where insulin retained its full biological activity as it was proven in vitro and in vivo. The insulin trapping NPs were in a size range of around 150-250 nm and exhibited a pH-dependent release. The type of solvent did not distinctly influence the particle properties or insulin stability but modified significantly the performance in vivo in rats, NPs prepared with glycofurol led to a bioavailability of F=1.4 ± 1.0% after oral administration while NPs prepared with PEG 300 were hardly efficient (F=0.3 ± 0.5%). In all cases t(max) was shifted to 2h compared to 1h after subcutaneous insulin solution. In general, we believe that the method presented here is a promising way to encapsulate sensitive drugs, especially for the production of peptide loaded NPs.
纳米粒子 (NPs) 已显示出一定的潜力，可以克服胃肠道中口服肽传递的缺点，如肽的稳定性和通透性低。载胰岛素 NPs 的制备是将 Eudragit RL 或 RS 溶解在不同的无毒聚乙二醇 (PEG) 衍生物中进行的。这些无毒溶剂的使用允许设计一种一步 NPs 制备方法，其中胰岛素在体外和体内均保持其完整的生物活性。胰岛素捕获 NPs 的粒径范围约为 150-250nm，并表现出 pH 依赖性释放。溶剂的类型并没有明显影响颗粒性质或胰岛素的稳定性，但对大鼠体内的性能有显著影响，用甘油醛制备的 NPs 经口服后生物利用度 F=1.4±1.0%，而用 PEG 300 制备的 NPs 几乎无效（F=0.3±0.5%）。在所有情况下，与皮下胰岛素溶液相比，t(max) 从 1 小时后转移到 2 小时后。总的来说，我们相信这里提出的方法是一种有前途的封装敏感药物的方法，特别是用于制备载肽的 NPs。
