Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 2/F, Laboratory Block 21 Sassoon Road, Hong Kong S.A.R., L2-08B, Pokfulam, China.
Advanced Biomedical Instrumentation Centre, Hong Kong Science Park, Hong Kong S.A.R, Shatin, China.
AAPS PharmSciTech. 2023 Apr 4;24(4):98. doi: 10.1208/s12249-023-02559-y.
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.
新型呼吸道传染病（如 COVID-19）的出现以及基于纳米粒子的 COVID-19 疫苗的迅速发展，最近重新激发了人们对设计可吸入纳米粒子药物传递系统作为下一代呼吸道治疗药物的浓厚兴趣。在气溶胶输送中各种可用的装置中，由于其使用简便、便携性高和长期稳定性好，干粉吸入器（DPI）更适合输送纳米粒子。尽管在开发吸入纳米粒子 DPI 制剂方面投入了研究工作，但迄今为止尚未批准任何此类制剂，这意味着从实验室到临床存在研究差距。本综述旨在通过强调临床前开发过程中的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了用于制造可吸入纳米粒子干粉制剂的制剂和颗粒工程策略。然后讨论了体外特性方法学中的一个重要但被忽视的方面，即如何将粉末性能与其生物命运联系起来。最后，突出了它们在临床转化中的主要挑战和策略。我们预计，对本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粒子干粉制剂的临床应用，从遥不可及的幻想变为现实。
