Cationic human defence peptides and cornea HSV‐1 infections: Results of a rabbit study

Abstract

In this study, we evaluated the potential of LiQD cornea glue supplemented with LL37‐derived peptide GF19, delivered through Silicium nanoparticles (SiNP) to prevent herpes simplex virus type 1 (HSV‐1) infection in a rabbit corneal model. SiNP‐GF19 was synthesized using a hydrophobic core, a hydrophilic shell, and a reactive surface that allowed covalent bonding to the collagen‐like peptides of our developed LiQD Cornea glue. Our results showed that SiNP‐GF19 was able to effectively release GF19 in a sustained manner, with approximately 60% of the peptide being released over 24 h. The remaining 40% of GF19 is trapped in the SiNP and can only be released upon complete degradation of the nanoparticles, which may occur via cellular uptake and enzymatic degradation. This ensures the prolonged release of GF19. The mechanism of action of GF19 against HSV‐1 may involve preventing the binding of the virus to host cells. Previous studies have shown that LL37, from which GF19 is derived, can block HSV‐1 binding to host cells, leading to decreased viral infection. However, in our study, we did not see reduced viral shedding, furthermore, nanoparticles coated with the GF19 peptide or nanoparticles themselves may have an eye irritant effect. Nevertheless, LiQD Cornea supplemented with SiNP‐GF19 or LiQD alone were effective in promoting corneal regeneration and healing. Specifically, it led to the formation of a relatively mature epithelium composed of 2–3 epithelial layers, expressing CK3 in the outermost epithelial layer, compared to the absence of epithelium or a monolayer of unstructured CK3‐negative epithelium in the cyanoacrylate adhesive control group. LiQD Cornea formulation without SiNP‐GF19 also displayed significantly lower α‐SMA staining than the rest of the experimental groups in the implant area, which overexpression is associated with abnormal extracellular matrix deposition and scar formation. In terms of nerve regeneration, all LiQD Cornea formulations showed βIII tubulin expression, indicating immature neuronal microtubule structures. In summary, all three experimental treatment strategies were significantly more effective compared to the cyanoacrylate adhesive control group, significantly smaller scar tissues without ingrown vascular networks were formed, though, only mild antiviral properties of SiNP‐GF19 were observed.