Take-away
A single drop of the lead pregabalin formulation reduces IOP by greater than 40%. IOP does not return to baseline until more than 30 hours post-application.
How does it work?
We identified the calcium voltage-gated channel auxiliary subunit alpha2delta 1 gene (Cacna2d1) as a modulator of IOP and demonstrated that pregabalin, a drug with high affinity and selectivity for CACNA2D1, lowered IOP in a dose-dependent manner.
What challenge needed to be solved?
When using standard pregabalin, IOP returned to baseline at 6 hours after dosing. The scientists wanted a formulation that could control IOP for 24 hours.
The solution
In the current study, the team develop a once daily topical pregabalin-loaded multiple water-in-oil-in-water microemulsion formulation to improve drug efficacy. We characterize our formulations using multiple in vitro and in vivo evaluations. Our lead formulation provides continuous release of pregabalin for up to 24 hours. Because of its miniscule droplet size (< 20 nm), our microemulsion has a transparent appearance and should not blur vision. It is also stable at one month of storage at temperatures ranging from 5 to 40 °C. Our formulation is nontoxic, as illustrated by a cell toxicity study and slit-lamp biomicroscopic exams. CACNA2D1 is highly expressed in both the ciliary body and the trabecular meshwork, where it functions to modulate IOP.
Conclusion
Although there were no significant differences in the magnitude of IOP reduction between the formulations we tested, a significant difference was clearly observed in their duration of action. Our multilayered microemulsion is a promising carrier that sustains the release and prolongs the duration of action of pregabalin, a proposed glaucoma therapeutic.
- Epub 2019 Nov 18
- PMID: 31714057
- DOI: 10.1021/acsnano.9b07214
- Abstract: Once Daily Pregabalin Eye Drops for Management of Glaucoma - PubMed
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Once Daily Pregabalin Eye Drops for Management of Glaucoma - PMC