Contact Lenses Delivering Nitric Oxide under Daylight for Reduction of Bacterial Contamination.

Mimimorena Seggio,Antonia Nostro,Fabiana Quaglia,Giovanna Ginestra,Salvatore Sortino

doi:10.3390/ijms20153735

Abstract

Ocular infection due to microbial contamination is one of the main risks associated with the wearing of contact lens, which demands novel straightforward strategies to find reliable solutions. This contribution reports the preparation, characterization and biological evaluation of soft contact lenses (CL) releasing nitric oxide (NO), as an unconventional antibacterial agent, under daylight exposure. A tailored NO photodonor (NOPD) was embedded into commercial CL leading to doped CL with an excellent optical transparency (transmittance = 100%) at λ ≥ 450 nm. The NOPD results homogeneously distributed in the CL matrix where it fully preserves the photobehavior exhibited in solution. In particular, NO release from the CL and its diffusion in the supernatant physiological solution is observed upon visible light illumination. The presence of a blue fluorescent reporting functionality into the molecular skeleton of the NOPD, which activates concomitantly to the NO photorelease, allows the easy monitoring of the NO delivery in real-time and confirms that the doped CL work under daylight exposure. The NO photoreleasing CL are well-tolerated in both dark and light conditions by corneal cells while being able to induce good growth inhibition of Staphylococcus aureus under visible light irradiation. These results may pave the way to further engineering of the CL with NOPD as innovative ocular devices activatable by sunlight.

Highlights

Contact lenses (CL), commonly employed to correct refractive errors, have been recently proposed as a drug delivery platform allowing constant and sustained drug levels in the eye [1,2,3]
Stimulated by our ongoing interest in the design and fabrication of nitric oxide (NO) photoreleasing constructs [16,20,21,22,23,24], we report the first example of contact lenses (CL) incorporating a tailored NO photodonor (NOPD) generating NO with a fluorescent reporting function under daylight exposure, its tolerability by corneal cells and photo-antibacterial activity against S. aureus
Excitation with visible light triggers NO photorelease from the nitroaniline moiety leading to the phenol derivative 2 as a stable byproduct

Summary

Introduction

Contact lenses (CL), commonly employed to correct refractive errors, have been recently proposed as a drug delivery platform allowing constant and sustained drug levels in the eye [1,2,3]. Strategies to generate ephemeral cytotoxic species to kill bacteria while wearing CL could represent a valid alternative to conventional antibiotic therapies. In this context, the use of nitric oxide (NO)-releasing agents is promising. Since NO has a well-recognized role in promoting corneal epithelial wound healing in cell and animal models [19] the concept of sustained NO release from bandage contact lenses could enlarge the arsenal of therapeutic tools available so far. Stimulated by our ongoing interest in the design and fabrication of NO photoreleasing constructs [16,20,21,22,23,24], we report the first example of CL incorporating a tailored NOPD generating NO with a fluorescent reporting function under daylight exposure, its tolerability by corneal cells and photo-antibacterial activity against S. aureus

Results and Discussion

Loading of the NOPD 1 in the CL

Bacterial Killing Assay

Phototoxicity Assay on Human Corneal Epithelial Cells

Conclusions

13. Nitric Oxide