Sin-China Nano Technology Center, State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029, PR China.
Int J Pharm. 2012 Jul 1;430(1-2):98-103. doi: 10.1016/j.ijpharm.2012.03.044. Epub 2012 Apr 1.
An innovative strategy of fabricating uniform spore like drug particles to improve pulmonary drug delivery efficiency was disclosed in the present study. Spore like particles were prepared through combination of high gravity controlled precipitation and spray drying process with insulin as model drug first, showing rough surface and hollow core. The shell of such spore-like particle was composed of nanoparticles in loose agglomerate and could form nanosuspension upon contacting antisolvent. Further characterization confirmed secondary structure and bio-activity was well preserved in spore like particles of insulin. Stable aerosol performance at different dosages with fine powder fraction (FPF) of 80% and comparable FPF (69-76%) for formulated powder were achieved, significantly higher than marketed product Exubera. On the other hand spore like particles of bovine serum albumin, lysozyme and salbutamol sulfate showed similar high FPF of 80%, regardless of different shape of primary nanoparticles, indicating various application of this new process in significant improvement of pulmonary drug delivery.
本研究提出了一种新颖的策略，通过高重力控制沉淀和喷雾干燥工艺将药物制成均一的孢子样颗粒，以提高肺部药物传递效率。首先以胰岛素为模型药物制备了孢子样颗粒，其具有粗糙的表面和空心核。这种孢子样颗粒的外壳由松散团聚的纳米颗粒组成，与反溶剂接触时可以形成纳米悬浮液。进一步的特性分析证实，胰岛素孢子样颗粒中二级结构和生物活性得以很好地保留。以不同剂量进行的稳定的气溶胶性能，其细粉分数（FPF）达到 80%，且与配方粉末的 FPF（69-76%）相当，明显高于市售产品 Exubera。另一方面，牛血清白蛋白、溶菌酶和硫酸沙丁胺醇的孢子样颗粒也表现出相似的高 FPF（80%），无论初级纳米颗粒的形状如何，这表明该新工艺在显著提高肺部药物传递方面具有广泛的应用。
