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Phosphorylcholine and KR12-Containing Corneal Implants in HSV-1-Infected Rabbit Corneas

Malhotra, Kamal; Buznyk, Oleksiy; Islam, Mohammad Mirazul; Edin, Elle; Basu, Sankar; Groleau, Marc; Dégué, Delali Shana; ... Griffith, May; + view all (2023) Phosphorylcholine and KR12-Containing Corneal Implants in HSV-1-Infected Rabbit Corneas. Pharmaceutics , 15 (6) , Article 1658. 10.3390/pharmaceutics15061658. Green open access

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Abstract

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.

Type: Article
Title: Phosphorylcholine and KR12-Containing Corneal Implants in HSV-1-Infected Rabbit Corneas
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/pharmaceutics15061658
Publisher version: https://doi.org/10.3390/pharmaceutics15061658
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: HSV-1 infection; corneal implant; RHCIII-MPC; KR12; nanoparticles; rabbits; regeneration
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology
URI: https://discovery.ucl.ac.uk/id/eprint/10172589
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