Nyambura Bildad K, Kellaway Ian W, Taylor Kevin M G
Pharmaceutics Department, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, UK.
Int J Pharm. 2009 Jun 22;375(1-2):114-22. doi: 10.1016/j.ijpharm.2009.03.031. Epub 2009 Apr 5.
Nanoparticles containing insulin have been produced by emulsification processes followed by freeze-drying. Purified nanoparticles were suspended in hydrofluoroalkane (HFA) 134a, using essential oils (cineole and citral) as suspension stabilizers to form pressurized metered dose inhaler (pMDI) formulations. The retention of insulin integrity after formulation processing was determined using high performance liquid chromatography (HPLC), size exclusion chromatography (SEC), circular dichroism (CD) and fluorescence spectroscopy. The results indicated that the native structure of insulin was retained after formulation processing. Aerosolization properties of the manufactured pMDI formulations were determined using a multi-stage liquid impinger. The results showed that the nanoparticles were suitable for peripheral lung deposition, with a fine particle fraction (FPF(<1.7 microm)) of approximately 45% (w/w). In conclusion, the pMDI formulations with nanoparticles containing insulin developed in this study have the potential to deliver protein therapeutics via inhalation for systemic action.
含胰岛素的纳米颗粒通过乳化工艺后冻干制备而成。将纯化的纳米颗粒悬浮于氢氟烷烃（HFA）134a中，使用精油（桉叶油素和柠檬醛）作为悬浮稳定剂以形成压力定量吸入器（pMDI）制剂。使用高效液相色谱（HPLC）、尺寸排阻色谱（SEC）、圆二色性（CD）和荧光光谱法测定制剂加工后胰岛素完整性的保留情况。结果表明，制剂加工后胰岛素的天然结构得以保留。使用多级液体冲击器测定所制备pMDI制剂的雾化特性。结果显示，纳米颗粒适用于外周肺沉积，细颗粒分数（FPF(<1.7微米)）约为45%（w/w）。总之，本研究中开发的含胰岛素纳米颗粒的pMDI制剂有潜力通过吸入递送蛋白质疗法以实现全身作用。
