Formulation of a Composite Nasal Spray Enabling Enhanced Surface Coverage and Prophylaxis of SARS‐COV‐2
Dr Richard J A Moakes, Dr Scott P Davies, Dr Zania Stamataki, Liam M Grover
Advanced Materials, doi:10.1002/adma.202008304
central nervous system, and respiratory diseases (Middle East Respiratory Syndrome (MERS), severe acute respiratory syndrome (SARS); [1] with the latest strain, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), receiving much attention due to its devastating impact within the 2020 pandemic. SARS-CoV-2, like all coronaviruses, contains large positive-strand RNA genomes packed within a helical capsid, all housed within a phospholipid bilayer envelope formed on budding. [2, 3] Associated with the viral membrane are 3 main proteins: membrane and envelope proteins, associated with assembly, and spike proteins. The spike proteins, which give rise to its corona shape, are essential for virus survival, mediating entry to the host cell. [4, 5] Additionally, the protein also plays a crucial role in determining host range and tissue tropism, alongside being responsible for inducing many of the host immune responses. [1] To date, facilitation of viral entry into a host cell is believed to arise through specific motifs within the spike protein, which strongly interact with Angiotensin-Converting Enzyme 2 (ACE2) receptors. [6, 7] ACE2 is known for its role in regulating oxygen/carbon dioxide transfer, commonly found within the respiratory epithelia. In particular, SARS-CoV-2 has been found to target the ciliated and goblet cells, [8] where subsequent viral shedding results in extensive viral loads, especially within the upper respiratory tract. [9] Inhaled air is primarily routed through the nose. Even though the nasal passages present the highest resistance to airflow, on average ≈10 000 L of air are inhaled by a healthy human per day. [10, 11] Only once this pathway becomes overloaded does the body switch to respiration through the mouth. [12, 13] For this reason, the nasal cavity supports two major roles: air conditioning, creating the correct levels of humidity and air temperature; and, removal of foreign particles including dust, airborne droplets and pathogens. [14] Anatomically, the nose consists of two cavities roughly 10 cm in length and half again in height, producing a total surface area of about 150 cm 2 . [15] Inspired air flows up through the nasal vestibule (nostril) and passes through the slit-like meatus structures (inferior, middle, and superior) and back through the nasopharynx. At a cellular level, the majority of the cavity consists of a typical airway epithelium, comprising of four main cell types: basal, ciliated/non-ciliated columnar, and goblet cells. The columnar Airborne pathogens pose high risks in terms of both contraction and transmission within the respiratory pathways, particularly the nasal region. However, there is little in the way of adequate intervention that can protect an individual or prevent further spread. This study reports on a nasal formulation with the capacity to combat such challenges, focusing on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Formulation of a..
(10 of 11) www.advmat.de www.advancedsciencenews.com initially cropped to a 2000 by 2000 px box visually centered around the spray pattern. Standard thresholding was applied to all images, and scale corrected equating 2000 px to 100%. Droplet analysis was conducted, and total coverage determined as a percentage of the whole image. Distributions were recorded as x/y coordinates and plotted relative to the central droplet. Infection/Transmission Analysis: The Vero cells were washed with PBS, dislodged with 0.25% Trypsin-EDTA (Sigma life sciences), and seeded into 96-well imaging plates (Greiner) at a density of 10 4 cells per well in culture media (Dulbecco's modified Eagle medium (DMEM) containing 10% FBS, 1% penicillin and streptomycin, 1% l-glutamine and 1% nonessential amino acids). Cells were incubated for 24 h to allow time for adherence. Virus or cells were treated with polymeric solutions, diluted in media, 1 h prior to infections. Cells were subsequently infected with SARS-CoV-2 virus England 2 stock 10 6 IUml −1 (kind gift from Christine Bruce, Public Health England) diluted 1/150 in culture media. Cells were fixed in ice-cold MeOH after infection. Cells were then washed in PBS and stained with rabbit anti-SARS-CoV-2 spike protein, subunit 1 (The Native Antigen Company), followed by Alexa Fluor 555-conjugated goat anti-rabbit IgG secondary antibody (Invitrogen, Thermofisher). Cell nuclei were visualized with Hoechst 33342 (Thermofisher). Cells were washed with PBS and..
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