Abstract
Purpose :
Dry eye disease has few treatment options outside of poorly absorbed eye drops that target only limited aspects of the immune system. Interleukin-4 (IL-4) has been shown to polarize macrophages from the inflammatory M1 phenotype - the phenotype prevalent in dry eye disease - to the anti-inflammatory M2 phenotype. IL-4 can be incorporated into a nanometer thick coating for mitigation of the foreign body reaction to implantable polypropylene mesh; however, application to other devices remains unclear. We hypothesize that this coating can be applied to silicone-hydrogel-based contact lenses with the goal of a sustained release profile of IL-4 for potential treatment of dry eye.
Methods :
Senofilcon A lenses were rinsed to remove residual storage buffer and then dipped into polymer solutions of opposite charges (dermatan sulfate complexed to IL-4 served as anion and chitosan served as cation) in order to build up 40 bilayers of IL-4 containing coating (Figure 1a). Immersion in alcian blue dye for 30 minutes followed by distilled water rinse was used to visualize surface coating. Coated lenses were incubated in solution containing chondroitinase ABC and chitosanase enzymes (or in solution void of enzymes) to mimic in-vivo conditions and collected at various time points for 28 days in order to determine release profile and kinetics of IL-4 release.
Results :
A uniform and conformal blue stain remained on lenses dipped in the oppositely charged polymers (when compared to a control, non-dipped lens), showing successful application of polymeric coating to the lens (Figure 1b). IL-4 release kinetics from a coated lens incubated with enzymes shows a sustained release of IL-4 over days (Figure 1c) vs no signal from an uncoated control lens. Interestingly, there is very little release of IL-4 from a coated lens in the absence of enzymes, showing that our coating is degraded primarily by enzymatic means.
Conclusions :
Our results support the hypothesis that our polymeric IL-4 releasing coating can be applied to contact lenses with a resulting sustained release of drug over days vs the transient burst release seen with eye drops. Future in-vivo work is necessary to determine if these coated lenses can help to mitigate inflammation associated with dry eye.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.