5. What Can LbL Nanocoating Contribute to the Prevention of Infectious Disease?

5.1. The Process of Layer-by-Layer (LbL) Nanocoating
LbL self-assembly of polyelectrolytes took its origin in the 1990s [78]. Poly(styrene-4-sulfonate), PSS, was one of the first polyanions employed for LbL self-assembly and remains widely utilized today. As polycation, an ammonium-containing polymer, poly(N,N-dimethylallylamine), PDDA, was successfully employed to create a multilayer structure comprising of alternating polyanion and -cation layers [79].
A series of proteins were also successfully employed as polycations namely cytochrome c, lysozyme, histone f3, myoglobin, and hemoglobin. By adjustment of the pH of the medium, amylase, glucose oxidase, and catalase were employed as polyanions [80]. DNA was also employed successfully as a polyelectrolyte for LL self-assembly [81].
LbL coating has also been employed to modify inorganic surfaces. Although many applications for these surface modifications are possible, only some antimicrobial examples are mentioned. Stainless steel surfaces were primed with an acrylate-based surfactant via electrografting. Subsequently, PSS and PDDA layers were coated in an alternating fashion. Lastly, a layer of chitosan was coated as an antibacterial layer against E. coli and S. aureus [82]. Silicone-based intraocular lenses (IOL) are commonly employed to replace the natural eye lens when it is damaged. The IOL can, however, allow adhesion of many kinds of bacteria and lead to post-operative infections with catastrophic effects in some patients. LbL nanocoating of the lenses with hyaluronic and chitosan had significant anti-adhesion and bactericidal effects that reduced the risk of postoperative infections [83,84].
The technique of LbL nanocoating is uncomplicated and requires relatively low concentrations of the polyelectrolytes to produce an efficient coat, often in the low nanometer range. A substrate for coating is required, a polycation and separate polyanion solution, and clean water as the washing liquid. Figure 3 illustrates the technique. Numerous polysaccharides, especially GAGs, are charged polyelectrolytes and the next section will elaborate on this.

5.2. Employment of Polysaccharides as LbL Materials
In this paper, the focus will fall only on common GAGs and other common polysaccharides such as chitosan. It was also noticed during our literature survey that the GAG, keratan sulfate has not been studied in LbL applications and can most probably be attributed to its production in the cornea, cartilage, and bone tissues which makes it fairly inaccessible. To date, the GAGs and other polysaccharides have not been employed widely in LbL nanocoating to specifically produce antiviral surfaces as is the case for antibacterial or antifungal coatings. Numerous publications have reported on the antibacterial surface application of polysaccharides via an LbL approach [85,86,87,88,89,90]. Table 1 lists some commonly utilized polysaccharides that have been employed in LbL nanocoatings and a non-exhaustive list of recent applications.
The reader should be able to realize that the LbL technique presents numerous possibilities for the application of polysaccharides as antiviral surfaces. Firstly, the polysaccharides, especially GAGs are abundantly available. Secondly, they can recognize and interact with proteins via a range of intermolecular forces including electrostatic, hydrogen bonding, and hydrophobic bonding [112]. Thirdly, the polysaccharides are biological molecules and in the case of LbL applications, need minimal or no modification to perform their intended function. Fourthly, fairly low quantities of material need to be deposited to coat the substrates. Lastly, they are biocompatible, biodegradable, and most renewable sources of material. It is very apt to illustrate the chemical structures of the GAGs and some other selected polysaccharides at this point. Figure 4 shows the structures based on the official IUPAC recommendations [113].
From Figure 4, it is observed that several anionic functional groups are available for electrostatic interaction, however, numerous hydroxyl and carbonyl groups are also available for hydrogen bonding. The successful application of polysaccharides as antimicrobials now leads us to the possible preventative measures against viruses.