Institute of Pharmaceutical Technology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
Int J Pharm. 2011 Jul 29;414(1-2):225-32. doi: 10.1016/j.ijpharm.2011.04.046. Epub 2011 May 6.
Nanoparticles consisting of human serum albumin (HSA) play an emerging role in the development of new drug delivery systems. Many of these protein-based colloidal carriers are prepared by the well-known desolvation technique, which has shown to be a robust and reproducible method for the laboratory-scale production of HSA nanoparticles. The aim of the present study was to upscale the ethanolic desolvation process utilizing the paddle stirring systems Nanopaddle I and II in combination with a HPLC pump in order to find the optimal conditions for the controlled desolvation of up to 2000 mg of the protein. For characterization of the HSA nanoparticles particle size, zeta potential as a function of the pH, polydispersity index and particle content were investigated. The particle content was determined by microgravimetry and by a turbidimetry to allow optimized in-process control for the novel desolvation technique. Furthermore the sedimentation coefficient was measured by analytical ultracentrifugation (AUC) to gain deeper insight into the size distribution of the nanoparticles. The formed nanocarriers were freeze dryed to achieve a solid preparation for long-term storage and further processing. Particles ranging in size between 251.2 ± 27.0 and 234.1 ± 1.5 nm and with a polydispersity index below 0.2 were achieved.
由人血清白蛋白 (HSA) 组成的纳米颗粒在新型药物输送系统的开发中发挥着新兴作用。许多基于蛋白质的胶体载体是通过众所周知的去溶剂化技术制备的，该技术已被证明是实验室规模生产 HSA 纳米颗粒的稳健且可重复的方法。本研究的目的是利用桨搅拌系统 Nanopaddle I 和 II 以及 HPLC 泵放大乙醇去溶剂化过程，以找到控制高达 2000 毫克蛋白质去溶剂化的最佳条件。为了对 HSA 纳米颗粒的粒径、zeta 电位与 pH 的关系、多分散指数和颗粒含量进行表征。通过微量天平法和浊度法测定颗粒含量，以实现新型去溶剂化技术的优化过程控制。此外，通过分析超速离心法 (AUC) 测量沉降系数，以更深入地了解纳米颗粒的粒径分布。将形成的纳米载体冷冻干燥以获得用于长期储存和进一步加工的固体制剂。粒径在 251.2 ± 27.0 和 234.1 ± 1.5nm 之间，多分散指数低于 0.2。
