Phosphorylcholine and KR12-Containing Corneal Implants in HSV-1-Infected Rabbit CorneasShow others and affiliations
2023 (English)In: Pharmaceutics, ISSN 1999-4923, E-ISSN 1999-4923, Vol. 15, no 6, article id 1658
Article in journal (Refereed) Published
Abstract [en]
Severe HSV-1 infection can cause blindness due to tissue damage from severe inflammation. Due to the high risk of graft failure in HSV-1-infected individuals, cornea transplantation to restore vision is often contraindicated. We tested the capacity for cell-free biosynthetic implants made from recombinant human collagen type III and 2-methacryloyloxyethyl phosphorylcholine (RHCIII-MPC) to suppress inflammation and promote tissue regeneration in the damaged corneas. To block viral reactivation, we incorporated silica dioxide nanoparticles releasing KR12, the small bioactive core fragment of LL37, an innate cationic host defense peptide produced by corneal cells. KR12 is more reactive and smaller than LL37, so more KR12 molecules can be incorporated into nanoparticles for delivery. Unlike LL37, which was cytotoxic, KR12 was cell-friendly and showed little cytotoxicity at doses that blocked HSV-1 activity in vitro, instead enabling rapid wound closure in cultures of human epithelial cells. Composite implants released KR12 for up to 3 weeks in vitro. The implant was also tested in vivo on HSV-1-infected rabbit corneas where it was grafted by anterior lamellar keratoplasty. Adding KR12 to RHCIII-MPC did not reduce HSV-1 viral loads or the inflammation resulting in neovascularization. Nevertheless, the composite implants reduced viral spread sufficiently to allow stable corneal epithelium, stroma, and nerve regeneration over a 6-month observation period.
Place, publisher, year, edition, pages
MDPI , 2023. Vol. 15, no 6, article id 1658
Keywords [en]
HSV-1 infection; corneal implant; RHCIII-MPC; KR12; nanoparticles; rabbits; regeneration
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:liu:diva-196869DOI: 10.3390/pharmaceutics15061658ISI: 001017745400001PubMedID: 37376106OAI: oai:DiVA.org:liu-196869DiVA, id: diva2:1791339
Note
Funding Agencies|Euronanomedicine 3 through the Fonds de la Recherche en Sante du Quebec [278653]; ERANET EuroNanoMed III [S-EURONANOMED-19-1/LSS-600000-2063]; Research Council of Lithuania; NSERC [RGPIN-2017-05410]; Swedish Research Council; UK MRC CDA fellowship [MR/T030968/1]; National Eye Institute of the National Institutes of Health [K99EY031373]; Fonds de Recherche Quebec Sante; Caroline Durand Foundation Research Chair in Cellular Therapy in the Eye; Canada Research Chair Tier 1 in Biomaterials and Stem Cells in Ophthalmology
2023-08-252023-08-252023-08-25