Antimicrobial Nitric Oxide Releasing Contact Lens Gels for the Treatment of Microbial Keratitis

• Published in: ACS applied materials & interfaces 2019-10, Vol.11 (41), p.37491-37501
• Main Authors: Aveyard, Jenny, Deller, Robert C, Lace, Rebecca, Williams, Rachel L, Kaye, Stephen B, Kolegraff, Keli N, Curran, Judith M, D’Sa, Raechelle A
• Format: Article
• Language: English
• Subjects: Anti-Infective Agents - chemistry; Anti-Infective Agents - pharmacology; Contact Lenses; Delayed-Action Preparations - chemistry; Delayed-Action Preparations - pharmacology; Epithelium, Corneal - metabolism; Epithelium, Corneal - microbiology; Epithelium, Corneal - pathology; Humans; Keratitis - drug therapy; Materials Testing; Nitric Oxide - chemistry; Nitric Oxide - pharmacology; Pseudomonas aeruginosa - growth & development; Pseudomonas Infections - drug therapy; Staphylococcal Infections - drug therapy; Staphylococcus aureus - growth & development
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.9b13958

Microbial keratitis is a serious sight threatening infection affecting approximately two million individuals worldwide annually. While antibiotic eye drops remain the gold standard treatment for these infections, the significant problems associated with eye drop drug delivery and the alarming rise in antimicrobial resistance has meant that there is an urgent need to develop alternative treatments. In this work, a nitric oxide releasing contact lens gel displaying broad spectrum antimicrobial activity against two of the most common causative pathogens of microbial keratitis is described. The contact lens gel is composed of poly-ε-lysine (pεK) functionalized with nitric oxide (NO) releasing diazeniumdiolate moieties which enables the controlled and sustained release of bactericidal concentrations of NO at physiological pH over a period of 15 h. Diazeniumdiolate functionalization was confirmed by Fourier transform infrared (FTIR), and the concentration of NO released from the gels was determined by chemiluminescence. The bactericidal efficacy of the gels against Pseudomonas aeruginosa and Staphylococcus aureus was ascertained, and between 1 and 4 log reductions in bacterial populations were observed over 24 h. Additional cell cytotoxicity studies with human corneal epithelial cells (hCE-T) also demonstrated that the contact lens gels were not cytotoxic, suggesting that the developed technology could be a viable alternative treatment for microbial  keratitis.