Ekaterina A. Trusova

Due to their availability and environmental friendliness, alginate polymers are widely used in pharmaceuticals and cosmetics. The most common type of alginate is derived from seaweed and is used to develop topical dosage forms, among other things. However, variability in the seaweed material can lead to instability in the physicochemical parameters. Biotechnologically produced alginate minimizes this drawback through controlled synthesis. However, unlike algal alginates, the safety profile of such polymers has not been well studied. When developing dosage forms intended for wound surfaces, safety is of primary importance. In this study, we developed enzybiotic compositions based on bacterial alginate as an excipient and a novel recombinant modified endolysin, LysSi3-LK, as an antibacterial agent, and assessed their antibacterial properties and safety profile. The study included an in vitro evaluation of the activity spectrum, as well as the cytotoxicity and biocompatibility, of gel and hydrogel compositions. It was demonstrated that bacterial alginate is acceptable for the encapsulation of endolysin. It exhibited medium cytotoxic effects on the HaCaT cells, which were significantly reduced by the LysSi3-LK addition. The migration of cells was diminished following exposure to the gel and hydrogel formulations. However, an improvement in biocompatibility was observed in the cell proliferation assay.

The development of new and effective antibacterials for pharmaceutical or cosmetic skin care that have a low potential for the emergence and expansion of bacterial resistance is of high demand in scientific and applied research. Great hopes are placed on alternative agents such as bactericidal peptidoglycan hydrolases, depolymerases, etc. Enzybiotic-based preparations are being studied for the treatment of various infections and, among others, can be used as topical formulations and dressings with protein-polysaccharide complexes. Here, we investigate the antibiofilm properties of a novel enzybiotic cocktail of phage endolysin LysSi3 and bacteriocin lysostaphin, formulated in the alginate gel matrix and its ability to control the opportunistic skin-colonizing bacteria Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae, as well as mixed-species biofilms. Our results propose that the application of SiL-gel affects different components of biofilm extracellular polymeric substances, disrupts the matrix, and eliminates the bacteria embedded in it. This composition is highly effective against biofilms composed of Gram-negative and Gram-positive species and does not possess significant cytotoxic effects. Our data form the basis for the development of antibacterial skin care products with a gentle but effective mode of action.