新型呼吸道感染的出现(例如,COVID-19)和基于纳米颗粒的COVID-19疫苗的迅速开发最近重新激发了人们对设计可吸入的基于纳米颗粒的药物递送系统作为下一代呼吸疗法的极大兴趣。在气溶胶输送的各种可用设备中,干粉吸入器(DPI)由于其使用简单而优选用于递送纳米颗粒,高便携性,和优越的长期稳定性。尽管致力于开发吸入式纳米颗粒DPI制剂的研究工作,迄今为止,尚未批准此类制剂,暗示长凳和床边之间存在研究间隙。这篇综述旨在通过强调临床前开发过程中重要但经常被忽视的问题来解决这一差距。我们首先概述和更新用于制造可吸入纳米颗粒基干粉制剂的制剂和颗粒工程策略。然后讨论了将粉末性能与其生物命运联系起来的体外表征方法中一个重要但被忽视的方面。最后,强调了其临床翻译中的主要挑战和策略。我们预计,对这篇综述中提出的现有知识空白的重点研究将加速可吸入纳米颗粒干粉的临床应用,从牵强的幻想到现实。
The emergence of novel respiratory infections (e.g., COVID-19) and expeditious development of nanoparticle-based COVID-19 vaccines have recently reignited considerable interest in designing inhalable nanoparticle-based drug delivery systems as next-generation respiratory therapeutics. Among various available devices in aerosol delivery, dry powder inhalers (DPIs) are preferable for delivery of nanoparticles due to their simplicity of use, high portability, and superior long-term stability. Despite research efforts devoted to developing inhaled nanoparticle-based DPI formulations, no such formulations have been approved to date, implying a research gap between bench and bedside. This review aims to address this gap by highlighting important yet often overlooked issues during pre-clinical development. We start with an overview and update on formulation and particle engineering strategies for fabricating inhalable nanoparticle-based dry powder formulations. An important but neglected aspect in in vitro characterization methodologies for linking the powder performance with their bio-fate is then discussed. Finally, the major challenges and strategies in their clinical translation are highlighted. We anticipate that focused research onto the existing knowledge gaps presented in this review would accelerate clinical applications of inhalable nanoparticle-based dry powders from a far-fetched fantasy to a reality.