Innovative Eye Drops With Enhanced Mucoadhesive Properties

HA-based eye drops are widely used today to treat the symptoms caused by eye dryness. However, HA linear solutions exhibit limited residence time on the ocular surface, mainly due to limited mucoadhesive properties. Noxelis, developed a complex formulation based on a co-crosslinked HA-modified chitosan, phosphatidylcholine and strong antioxidants. This innovative formulation was designed for patients with moderate to severe dry eye to answer major patient concern and improve the residence time on the ocular surface via a complex and concentrated formulation that enhanced mucoadhesive properties. Creating both increase of residence time, a better affinity with the ocular surface/cornea to optimize the relief of dry eye patients.

The eye surface is covered by mucins, negatively charged glycoproteins that are intimately linked to the corneal surface. It is an essential component of the lachrymal fluid. The presence of specific polymers in artificial tears is crucial to improve the mucoadhesive properties and consequently the efficacy of such treatment. HA and mucins can interact via entanglements as well as hydrogen bounding and mucoadhesion is optimized with high HA concentration. 

To enhance the mucoadhesive properties of NOX-01 eye drops, we employed the following method: (i) use a very high HA concentration compared to commercial products and (ii) add positively-charged components that are shown to be crucial when it comes to mucoadhesion, by their capacity to form multiple electrostatic interactions with mucins.  

The objective of this study was to characterize the mucoadhesive properties of eye drop formulations via rheological measurements. The present method is based on the method proposed in the literature.^1,2

 The mucoadhesiveness of the samples is expressed as: 

∆%=(η_(muc+OD)-(η_muc+η_OD ))/((η_muc+η_OD ) )×100

The results showed that most of the commercial products have a low viscosity (< 20cP) and which does not vary much with the shear rate, thus exhibiting a Newtonian behaviour. Two of them have a higher viscosity, around 70 cP and 3000 cP at low shear rate respectively, and with a shear-thinning behaviour, which is also the case of NOX-01 that has a viscosity at low shear rate about 60 cP and a shear thinning behaviour, with a viscosity of 15-20cP at blinking shear rate (> 1000 ^s-1). Interestingly, while performing the mucoadhesive tests, we demonstrated that even if NOX-01 does not have the higher viscosity, its mucoadhesive index was higher than the other products and the mucoadhesion properties were maintained even at high shear rate.

We analyzed the mucoadhesive properties of several commercial eye drops and compared it with NOX-01 formulation. The viscosity of NOX-01 was designed to get the best compromise between optimum lubrication properties and comfort for the patient. Also, we could demonstrate that the selection of the right components and concentrations led to enhanced mucoadhesive properties.

It was also demonstrated a superior mucoadhesion versus competitors. Therefore, we can assume that the remanence of NOX-01 on the ocular surface will be superior, in particular on damaged ocular surface caused by refractive surgery as LASIK. This formulation is expected to improve and accelerate the corneal regeneration.