Caveat: In the US, pregabalin is a Schedule V controlled substance under the Controlled Substances Act of 1970 It is a Class C controlled substance in the UK.
Abstract (edited by FitEyes)
Elevated intraocular pressure (IOP) is the most significant risk factor contributing to visual field loss in glaucoma. Unfortunately, the deficiencies associated with current therapies have resulted in reduced efficacy, several daily dosings, and poor patient compliance.
Previously, 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. Unfortunately, IOP returned to baseline at 6 h after dosing when using our initial formulation.
In the current study, we develop a once daily topical pregabalin-loaded multiple water-in-oil-in-water microemulsion formulation to improve drug efficacy. We characterize our new formulations using multiple in vitro and in vivo evaluations.
Our lead formulation provides continuous release of pregabalin for up to 24 h. 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.
A single drop of our lead pregabalin formulation reduces IOP by greater than 40%, which does not return to baseline until more than 30 hour post-application.
Although there were no significant differences in the amplitude of IOP reduction between the pregabalin 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.
- Publication date: 2019 Nov 18
- Journal: ACS Nano. 2019 Dec 24;13(12):13728-13744
- PMID: 31714057
- DOI: 10.1021/acsnano.9b07214
Keywords: XRD; corneal permeability; cytotoxicity; glaucoma; immunohistochemistry; microemulsion; stability.