Xi Jinxiang, Lei Lameng Ray, Zouzas William, April Si Xiuhua
Department of Biomedical Engineering University of Massachusetts Lowell Massachusetts USA.
Amphastar Pharmaceuticals, Inc Rancho Cucamonga California USA.
MedComm (2020). 2021 Dec 14;2(4):569-586. doi: 10.1002/mco2.101. eCollection 2021 Dec.
The nose is the initial site of viral infection, replication, and transmission in the human body. Nasally inhaled vaccines may act as a promising alternative for COVID-19 management in addition to intramuscular vaccination. In this review, the latest developments of nasal sprays either as repurposed or antiviral formulations were presented. Nasal vaccines based on traditional medicines, such as grapefruit seed extract, algae-isolated carrageenan, and Yogurt-fermenting , are promising and under active investigations. Inherent challenges that hinder effective intranasal delivery were discussed in detail, which included nasal device issues and human nose physiological complexities. We examined factors related to nasal spray administration, including the nasal angiotensin I converting enzyme 2 (ACE2) locations as the delivery target, nasal devices, medication translocation after application, delivery methods, safety issues, and other nasal delivery options. The effects of human factors on nasal spray efficacy, such as nasal physiology, disease-induced physiological modifications, intersubject variability, and mucociliary clearance, were also examined. Finally, the potential impact of nasal vaccines on COVID-19 management in the developing world was discussed. It is concluded that effective delivery of nasal sprays to ACE2-rich regions is urgently needed, especially in the context that new variants may become unresponsive to current vaccines and more refractory to existing therapies.
鼻子是病毒在人体中感染、复制和传播的初始部位。除了肌肉注射疫苗外，鼻内吸入疫苗可能是管理新冠疫情的一种有前景的替代方法。在这篇综述中，介绍了作为重新利用或抗病毒制剂的鼻喷雾剂的最新进展。基于传统药物的鼻用疫苗，如葡萄柚籽提取物、藻类分离的卡拉胶和酸奶发酵剂，很有前景且正在积极研究中。详细讨论了阻碍有效鼻内给药的内在挑战，包括鼻用装置问题和人类鼻子生理复杂性。我们研究了与鼻喷雾剂给药相关的因素，包括作为给药靶点的鼻血管紧张素I转换酶2（ACE2）位置、鼻用装置、给药后药物转运、给药方法、安全性问题以及其他鼻内给药选择。还研究了人为因素对鼻喷雾剂疗效的影响，如鼻腔生理学、疾病引起的生理改变、个体间变异性和黏液纤毛清除功能。最后，讨论了鼻用疫苗对发展中世界新冠疫情管理的潜在影响。得出的结论是，迫切需要将鼻喷雾剂有效递送至富含ACE2的区域，尤其是在新变种可能对现有疫苗无反应且对现有疗法更具耐药性的情况下。
