Enhanced topical drug delivery
Recently, we have been investigating the use of a novel semi-fluorinated alkane (SFA) drug delivery technology (EyeSol, Novaliq) as a vehicle to deliver cannabinoids to the ocular surface. This class of molecules has a number of advantages as an eye drop.
EyeSol-based drops contain no water, so they mix well with lipophilic substances, including cyclosporine and THC, and allow them to remain solubilised instead of separating out in the bottle. They have a very low surface tension so a drop on the eye rapidly forms a very thin layer, giving it spreading properties that are far superior to an aqueous eye drop (Figure 1).
These properties should help to distribute a drug across the uneven ocular surface without the drug being immediately drained or spilling out of the eye as excess aqueous. SFA molecules are metabolically inert and do not interact with the immune system. Finally, they have a refractive index similar to water, so they do not disturb vision the way oil emulsions of lipophilic ingredients can.
In several observational trials we conducted, q.i.d. treatment with an EyeSol delivery vehicle alone resulted in a highly significant reduction in corneal staining and a 20-point improvement in OSDI scores after just six weeks.6 We thought that if this vehicle could be combined with a compound like THC for pain and inflammation, it could be very beneficial in dry eye treatment.
We began to conduct experiments using an established mouse model for dry eye disease that relies on behavioural testing methods to determine pain levels, as well as other testing methods (Figure 2). We compared a group treated with EyeSol THC eye drops to a control group treated with topical cyclosporine.
One-year results of these preclinical studies suggest that the drop is at least as effective as cyclosporine and may have dual or even triple mechanisms of action, including lubrication, anti-inflammation and pain reduction. Although we continue to evaluate various parameters, the pharmacodynamics thus far are very promising.
We are fairly confident that topical application of THC dissolved in EyeSol will not result in any measurable systemic effects. The first human clinical trials in dry eye disorder are expected to begin in the second half of 2018.