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Monica M Jablonski, Doaa N. Maria, Mohamed M. Ibrahim; Novel Topical Formulation Reduces IOP for up to 34 Hours After a Single Dose. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5681.
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© ARVO (1962-2015); The Authors (2016-present)
Elevated IOP is one of the most significant risk factors of visual field loss in glaucoma, therefore IOP reduction is the first-line therapeutic option. Unfortunately, current IOP-lowering therapies have multiple deficiencies including rapid drainage, short corneal contact time and minimal corneal penetration, all of which lead to reduced efficacy and poor patient compliance. Our study was designed to develop a novel topical formulation as a once-daily IOP-lowering drop.
In our recent systems genetics study, we identified Cacna2d1 as a novel modulator of IOP and confirmed that modulation of the activity of the gene product, CACNA2D1, lowers IOP in a dose-dependent manner (Nat Comm 2017; 8:1755). To expand on this finding and move toward a once daily IOP-lowering drop, we engineered a W/O/W microemulsion containing a BCS class I drug (highly soluble and highly permeable), and characterized the formulation using multiple in vivo and in vitro evaluations.
Our microemulsion is multilayered and was engineered using highly biocompatible components with in situ gelling properties that improve bioadhesion, control corneal penetration and provide continuous release of drug for up to 24h. Because our microemulsion has a miniscule particle size (20nm), it is transparent and does not blur vision. Our formulation is safe, as demonstrated with MTT and slit-lamp biomicroscopic exams. It also markedly enhances the efficacy of the drug. Using Dutch belted rabbits, we effectively demonstrate that a single drop of our microemulsion can induce a 38.7% reduction in IOP that returned to baseline at 34h after application (AUC=169.3mmHg.hr). In the absence of our microemulsion, the same drug produced only a 26.7% IOP reduction that returned to baseline at 10h (AUC=38mmHg.hr).
We have engineered a novel topical formulation that will support once daily dosing of drug as an IOP-lowering therapy. It is safe and biocompatible. Moreover, it greatly improves IOP-lowering efficacy both in terms of amplitude and duration of response, which is supported by its increased mucoadhesive properties, controlled corneal permeability, miniscule particle size, and sustained release behavior. If replicated in prospective clinical trials, our novel formulation could revolutionize glaucoma therapy.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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