Tayyar Yaman, Idris Adi, Yassine Hadi
Biomedical Research Centre, QU Health, Qatar University, Doha, Qatar.
Institute for Biomedicine and Glycomics, Griffith University, Brisbane, QLD, Australia.
Int J Nanomedicine. 2025 Jun 23;20:8085-8099. doi: 10.2147/IJN.S517385. eCollection 2025.
Delivery of nano-therapeutics through the nasal route offers a promising approach for several applications, including intranasal conditions, pulmonary delivery, brain targeting, and vaccination. Despite its potential, this method faces significant challenges, including overcoming the mucosal barrier, ensuring consistent absorption, controlling the deposition area, and managing immunogenic responses. This review provides a comprehensive overview of the current state of nasally delivered lipid nanoparticles (LNPs) for gene medicine, focusing on the specific barriers encountered in this delivery route and strategies to overcome them. We examine how formulation composition affects stability during aerosolization, analyze the impact of particle characteristics on mucociliary clearance, and evaluate interactions with the lung surfactant layer. The review also compares delivery devices including metered-dose inhalers, dry powder inhalers, and nebulizers, highlighting how device selection influences LNP integrity and deposition patterns. Furthermore, we explore potential safety considerations with intranasal LNPs and propose approaches to mitigate adverse effects. By addressing these challenges with evidence-based strategies, this review aims to advance the development and clinical application of intranasal and pulmonary LNP delivery systems for gene-based therapeutics and vaccines.
通过鼻腔途径递送纳米治疗药物为多种应用提供了一种有前景的方法，包括鼻腔疾病治疗、肺部递送、脑靶向和疫苗接种。尽管具有潜力，但这种方法面临重大挑战，包括克服黏膜屏障、确保一致的吸收、控制沉积区域以及管理免疫原性反应。本综述全面概述了用于基因治疗的经鼻腔递送脂质纳米颗粒（LNPs）的现状，重点关注该递送途径中遇到的特定障碍以及克服这些障碍的策略。我们研究制剂组成如何影响雾化过程中的稳定性，分析颗粒特性对黏液纤毛清除的影响，并评估与肺表面活性物质层的相互作用。该综述还比较了包括定量吸入器、干粉吸入器和雾化器在内的递送装置，强调了装置选择如何影响LNP的完整性和沉积模式。此外，我们探讨了经鼻腔LNPs潜在的安全性考虑因素，并提出减轻不良反应的方法。通过用基于证据的策略应对这些挑战，本综述旨在推动用于基于基因的治疗和疫苗的经鼻腔和肺部LNP递送系统的开发和临床应用。
