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

Abstract

The COVID-19 global pandemic, as well as the widespread persistence of influenza and the common cold, create the need for new medical devices such as nasal sprays to prevent viral infection and transmission. Carrageenan, a sulfated polysaccharide, has a broad, non-pharmacological antiviral capacity, however it performs poorly in two key areas; spray coverage and mucoadhesion. Therefore gellan, another polysaccharide, was investigated as an excipient to improve these properties. It was found that viscoelastic relaxation time was the key predictor of spray coverage, and by reducing this value from 2.5 to 0.25 s, a mix of gellan and carrageenan gave more than four times the coverage of carrageenan alone (p < 0.0001). Gellan also demonstrated enhanced adhesion to a mucus analog that increased significantly with time (p < 0.0001), suggesting the development of specific gellan–mucin interactions. This property was conferred to carrageenan on mixing the two polymers. Together, this data suggests that gellan is a promising excipient to improve both sprayability and mucoadhesion of carrageenan for use in antiviral nasal sprays.

Self‐Delivering Microstructured Iota Carrageenan Spray Inhibits Fibrosis at Multiple Length Scales

“…[44] This has been overcome previously by blending with another polysaccharide to disrupt the bulk network. [44] Carrageenans undergo gelation by transitioning from random Figure 6. Iota carrageenan sequesters TGFβ1.…”

Recent Advances in Mucoadhesive Interface Materials, Mucoadhesion Characterization, and Technologies

“…Nasal COVID-19 vaccines can eliminate the spread better than the standard vaccines since the nasal mucosa is often the initial site of infection. [160,161] Figure 8a,b shows that pristine or modified polysaccharides can be promising candidates for nasal mucoadhesion and subsequent drug delivery. In fact, Figure 8b shows that a natural polymer, carrageenan, a sulfated polysaccharide having a broad antiviral capacity with poor mucoadhesion properties can be modified with gellan to adhere very well to nasal mucus and can be used in antiviral nasal sprays.…”

“…In fact, Figure 8b shows that a natural polymer, carrageenan, a sulfated polysaccharide having a broad antiviral capacity with poor mucoadhesion properties can be modified with gellan to adhere very well to nasal mucus and can be used in antiviral nasal sprays. [161] In Figure 8b, a drop flow adhesion test system is shown schematically. In such a test, drops of the polymer solution are deposited onto a gelatin only or mucin gelatin surface and are allowed to adhere for 0, 120, or [138] Experimental measurement uncertainties were within 10%.…”

“…Reproduced under the terms of the CC‐BY 4.0 license. [ 161 ] Copyright 2021, The Authors, published by Frontiers in Medical Technology. c) Mucoadhesion mechanism between thiolated polymer and the intestinal mucin layer due to disulfide bond formation.…”

“…The authors also demonstrated that for efficient nasal spray coverage, the viscoelastic relaxation time was the key, and by reducing this value from 2.5 to 0.25 s, a mix of gellan and carrageenan polymers had more than four times the coverage of carrageenan alone. [ 161 ] In a similar work, Mackaya‐Navarro et al. [ 162 ] modified sodium alginate to improve its mucoadhesion, upon thiolation of alginate, its mucoadhesion can be improved as schematically shown in Figure 8c.…”