Formulation of a composite nasal spray enabling enhanced surface coverage and prophylaxis of SARS-COV-2

Abstract

Airborne pathogens pose high risks in terms of both contraction and transmission within the respiratory pathways, in particular the nasal region. Although knowledge of airborne transmission has long been known, there is little in the way of adequate intervention that can protect the individual, or even prevent further spread. This study focuses on a nasal applicant with the capacity to combat such issues, by focussing on the SARS-CoV-2 virus. Formulation of a spray containing polysaccharides known for their mucoadhesive properties was undertaken and characterised for their mechanical, spray patterns and antiviral properties. The ability to engineer key behaviours such as yielding have been shown, through systematic understanding of a composite mixture containing two polymers: gellan and λcarrageenan. Furthermore, spray systems demonstrated highly potent antiviral capacities, resulting in complete inhibition of the virus when studied for both prophylaxis and prevention of spread. Finally, a mechanism has been proposed to explain such findings. Therefore, demonstrating the first fully preventative device, targeted to protect the lining of the upper respiratory pathways.

Carrageenan-containing over-the-counter nasal and oral sprays inhibit SARS-CoV-2 infection of airway epithelial cultures

“…The anti-SARS-CoV-2 activity of purified ι-/κ-carrageenans was in the same range, showing that these polymers are the responsible antiviral factors in products A and B. Carrageenans have previously been reported to have broad antiviral activity against, e.g., influenza A, dengue, hepatitis A, and rhino- and common cold coronaviruses in cell culture and some clinical studies ( 16 , 22 , 24 , 38 ), and application of carrageenan-containing nose sprays to combat SARS-CoV-2 has been suggested ( 39 – 41 ). Four preprint articles support our findings and show that a mixture of gellan and λ-carrageenan ( 42 ) or ι-carrageenan inhibits SARS-CoV-2 infection ( 25 , 43 , 44 ). The antiviral effect of carrageenans is most likely based on decreased viral attachment to and entry into target cells.…”

Viral inhibitors derived from macroalgae, microalgae, and cyanobacteria: A review of antiviral potential throughout pathogenesis

“…These compounds act at different points during SARS-CoV-2 pathogenesis. Clinical trials examining the therapeutic potential of a carrageenan-based anti-SARS-CoV-2 nasal spray are underway in the USA, with similar research taking place in the UK [ 70 , 71 ]. Thus, algae-derived compounds may serve as a prophylactic measure, similar to wearing a mask, to prevent SARS-CoV-2 infection by preventing virions from entering the respiratory tract.…”

“…Multiple carrageenan-based nasal sprays are currently marketed in Europe and Canada [ 68 , 69 ]; additional research and investment could provide a massive protective effect to vulnerable populations in other countries around the world. A clinical trial evaluating the prophylactic effect of a carrageenan nasal spray against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently underway in the United States [ 70 ] and similar efforts to develop an anti-SARS-CoV-2 carrageenan nasal spray are being made in the UK [ 71 ].…”

Low Acyl Gellan as an Excipient to Improve the Sprayability and Mucoadhesion of Iota Carrageenan in a Nasal Spray to Prevent Infection With SARS-CoV-2

“…Although emerging technologies are being seen to help protect this area (23)(24)(25), adequate devices to prevent contraction of airborne viruses and stop further spread are still needed. One option for such a device is a spray formulation, applied directly to the nasal cavity, to bolster the natural antiviral function of the mucosa (26). Such a formulation, in addition to exhibiting a potent ability to prevent viral infection and transmission, should give a large, even spray plume, to fully coat the surface of the nasal cavity, and adhere to the mucus layer, so that it can be retained and extend antiviral protection (Figure 1).…”

“…Further, carrageenans have been shown to possess a broad, non-specific antiviral capacity, able to inhibit viruses including the common cold (28)(29)(30), influenza (31,32), and SARS-CoV-2 (32)(33)(34). However, at clinically relevant viscosities, carrageenan demonstrates poor sprayability (26). An excipient is therefore required to improve the material properties of carrageenan for use as an antiviral spray device.…”