Spray formulations that can either inactivate SARS‐CoV‐2 or block its entry into cells will be promising to decrease viral load in the nose, thus preventing the viral spread to the lung or surrounding people. Nasal sprays can act as a potent alternative for COVID‐19 therapeutics and vaccination. Human nasal passages are the initial dominant sites of viral invasion, replication, and transmission. There exists a pressing need to develop inhalation‐based vaccines/therapies to assist COVID‐19 management, which should take into account the infection onset (viral entry), progression (viral shedding), and exacerbation, where quick viral replication and cytokine storms in the pulmonary alveoli lead to pneumonia and respiratory failure. However, there are only a handful of vaccines that have been approved or via emergence use authorization (EUA) for vaccination/treatment of COVID‐19, all of which are intravenously administered. Vaccines and therapeutics have been actively developed since the pandemic all over the world. It has been proven to be highly challenging to prevent viral transmission because of its high transmissibility and constantly evolving variants. Up to the moment (October 15, 2021), it has caused 239,437,517 confirmed cases and 4,879,235 deaths, while a total of 6,495,672,032 vaccine doses have been administered. Advantages of nasally inhaled therapeutics and vaccination for COVID‐19ĬOVID‐19 is a highly transmissible respiratory infectious disease due to the SARS‐CoV‐2 virus. 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.ġ.1. Finally, the potential impact of nasal vaccines on COVID‐19 management in the developing world was discussed. 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. 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. Inherent challenges that hinder effective intranasal delivery were discussed in detail, which included nasal device issues and human nose physiological complexities. Nasal vaccines based on traditional medicines, such as grapefruit seed extract, algae‐isolated carrageenan, and Yogurt‐fermenting Lactobacillus, are promising and under active investigations. In this review, the latest developments of nasal sprays either as repurposed or antiviral formulations were presented. ![]() ![]() Nasally inhaled vaccines may act as a promising alternative for COVID‐19 management in addition to intramuscular vaccination. The nose is the initial site of viral infection, replication, and transmission in the human body.
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