Respiratory Technology, Woolcock Institute of Medical Research, NSW 2006, Australia; Discipline of Pharmacology, Sydney Medical School, The University of Sydney, NSW 2006, Australia.
Respiratory Technology, Woolcock Institute of Medical Research, NSW 2006, Australia; Discipline of Pharmacology, Sydney Medical School, The University of Sydney, NSW 2006, Australia.
Pharmacol Ther. 2014 Dec;144(3):235-52. doi: 10.1016/j.pharmthera.2014.05.003. Epub 2014 May 15.
During the process of inhalable formulation development a deep knowledge of the physicochemical characteristics of the drug and formulation components and the biological properties of the airways is necessary. For example, the solubility and lipophilicity of a drug may affect therapeutic efficacy by changing the residence time of the microparticles at the airway surface. Furthermore, the properties of microparticles, such as shape, size and density, as well as the diseases of the respiratory tract, delivery device and inhalation manoeuvre will have an impact on where these microparticles are deposited. The airway epithelium is involved in the pathogenesis and treatment of respiratory diseases. Epithelial cells are directly exposed to the environment and respond to xenobiotics. In some cases, they are the site of action for drug molecules or the drug molecules might need to be transported across the epithelium to arrive at the site of action. The drug particles deposited on the respiratory epithelia have to interact with the mucus lining, dissolve and get transported through this layer. Despite advances in in vitro testing of respiratory epithelial permeability, there is little known about how and where drugs are absorbed at a cellular level and how long they reside in the lung. Therefore, pulmonary permeability assessment of drugs may provide insights that will allow formulations to be developed with optimised therapeutic outcomes. This review focuses on the integration of these physicochemical characteristics with the biological factors to provide a better understanding of the fate of microparticles after deposition on the epithelial cells.
在可吸入制剂的开发过程中，需要深入了解药物和制剂成分的物理化学特性以及呼吸道的生物学特性。例如，药物的溶解度和脂溶性可能会通过改变微粒子在气道表面的停留时间来影响治疗效果。此外，微粒子的特性，如形状、大小和密度，以及呼吸道疾病、输送装置和吸入操作，都会影响这些微粒子的沉积位置。气道上皮细胞参与了呼吸道疾病的发病机制和治疗。上皮细胞直接暴露于环境中，并对异物做出反应。在某些情况下，它们是药物分子的作用部位，或者药物分子可能需要穿过上皮细胞到达作用部位。沉积在呼吸道上皮细胞上的药物颗粒必须与黏液内层相互作用、溶解并穿过这一层。尽管在体外测试呼吸道上皮细胞通透性方面取得了进展，但对于药物在细胞水平上是如何以及在何处被吸收以及它们在肺部停留多长时间，人们知之甚少。因此，对药物的肺部通透性进行评估可以提供一些见解，从而可以开发出具有优化治疗效果的制剂。这篇综述的重点是将这些物理化学特性与生物学因素相结合，以更好地了解微粒子沉积在上皮细胞后的命运。
