Particle engineering approaches to control the interaction of medicinal aerosols with the lung environment following inhalation

摘要：气雾剂广泛应用于呼吸系统疾病的治疗。因此，人们对活性药物成分和给药装置如何影响颗粒沉积和患者结局进行了重要研究。然而，关于呼吸系统中水蒸气相互作用对特定的物理化学气溶胶性质的依赖性的研究仍然有限。因此，它们对肺环境中吸湿性生长、溶解和聚集的影响往往被忽视。本项目的重点是通过干粉吸入器输送固体药物颗粒，并回顾了可能支持呼吸系统湿度中气溶胶动力学的一些颗粒特性。此外，作为回应，提出了一种利用微流控结晶技术来制备具有明显特征和性质的单分散模型粒子的新方法。随后对模型颗粒的研究将允许确定微丝性质，如大小、表面积和结晶度，对固体药物颗粒与人体肺部水分相互作用的影响程度。通过这样做，它将加强对呼吸系统中气雾剂动力学基本基本原理的了解，并有助于优化气雾剂药物输送技术。

Abstract: Aerosol therapeutics are widely used in the treatment of respiratory and systemic disease. As such, significant research has gone into how the active pharmaceutical ingredient and delivery device affect particle deposition and patient outcomes. However, there remains limited research on the dependency of water vapour interactions, in the respiratory system, on specific, physicochemical aerosol properties. Consequently, their influence on hygroscopic growth, dissolution and agglomeration within the lung environment is often overlooked. This project focuses on the delivery of solid drug particles by dry powder inhalers and reviews some of the particle properties that may underpin aerosol dynamics in the humidity of the respiratory system. Furthermore, in response, a novel way to produce monodisperse model particles with distinct characteristics and properties using microfluidic crystallisation techniques is presented. The subsequent investigation of the model particles will allow for the determination of the extent of impact that micromeritic properties, such as size, surface area and crystallinity, have on the interaction of solid drug particles with moisture in the human lung. In doing so, it will enhance the understanding of the fundamental, underlying principles of aerosol dynamics in the respiratory system and contribute to the potential for optimisation of aerosol drug delivery techniques.