Department of Bioengineering, Hanyang University, Seoul 133-791, Republic of Korea.
J Control Release. 2011 Feb 28;150(1):56-62. doi: 10.1016/j.jconrel.2010.11.001. Epub 2010 Nov 9.
Inhaling corticosteroids, such as budesonide (BD), is the most common treatment for asthma. However, frequent steroid administration is associated with many side effects. We hypothesized that porous microparticles containing BD could provide an effective treatment method for asthma, as the sustained delivery of corticosteroid and a reduced number of doses could be achieved using porous polymeric microparticles. Porous microparticles were prepared from poly(lactic-co-glycolic acid) (PLGA) by a water-in-oil-in-water double emulsion method with ammonium bicarbonate as the porogen. Varying the porogen concentration controlled the morphology, particle size, and pore size of the PLGA microparticles, with particle size and pore size increasing as the porogen concentration increased. The BD loading efficiency in the porous PLGA microparticles was about 60%, and BD was released from the porous microparticles in a sustained manner for 24h in vitro. Lung uptake efficiency of the porous PLGA microparticles in mice was significantly higher than that of non-porous PLGA microparticles. Budesonide-loaded porous PLGA microparticles were delivered to asthmatic mice, and the numbers of inflammatory cells in bronchoalveolar lavage (BAL) fluid and tissue sections were significantly reduced when the drug was administrated every 3days. We also found significantly reduced bronchial hyperresponsiveness of asthmatic mice after treatment with budesonide-loaded porous PLGA microparticles. This approach to controlling the porous structure of polymeric microparticles, as well as the release behavior of drugs from the microparticles, could have useful applications in the pulmonary delivery of many therapeutic drugs.
吸入皮质类固醇，如布地奈德（BD），是治疗哮喘最常用的方法。然而，频繁使用类固醇会引起许多副作用。我们假设含有 BD 的多孔微球可以为哮喘提供一种有效的治疗方法，因为通过多孔聚合物微球可以实现皮质类固醇的持续释放和减少剂量。多孔微球是通过水包油包水双乳液法用碳酸氢铵作为致孔剂从聚（乳酸-共-羟基乙酸）（PLGA）制备的。改变致孔剂的浓度可以控制 PLGA 微球的形态、粒径和孔径，随着致孔剂浓度的增加，粒径和孔径增大。多孔 PLGA 微球中 BD 的载药效率约为 60%，BD 可以在体外以持续的方式释放 24 小时。多孔 PLGA 微球在小鼠肺部的摄取效率明显高于非多孔 PLGA 微球。将载有布地奈德的多孔 PLGA 微球递送至哮喘小鼠，当每 3 天给药时，支气管肺泡灌洗液（BAL）和组织切片中的炎症细胞数量明显减少。在用载有布地奈德的多孔 PLGA 微球治疗后，我们还发现哮喘小鼠的支气管高反应性明显降低。这种控制聚合物微球多孔结构和药物从微球中释放行为的方法，可能在许多治疗药物的肺部给药中具有有用的应用。
