- PMID: 35932931
- DOI: 10.1016/j.ijpharm.2022.122078
Abstract
The ocular endocannabinoid system (ECS) including enzymes and CB1/CB2 receptors determines various substantial effects, such as anti-inflammatory activity and reduction of the intraocular pressure (IOP). The modulation of 2-arachidonoylglycerol (2-AG) levels obtained via MAGL inhibition is considered as a promising pharmacological strategy to activate the ECS. Within the scope of this study, the effect of a selective monoacylglycerol lipase (MAGL) inhibitor (MAGL17b) was investigated by measuring the IOP reduction in normotensive rabbits after performing a solubilisation process of the molecule with non-ionic surfactants, to produce suitable eye drops containing the highest possible concentration of the drug. Furthermore, the study involved the evaluation of cytotoxicity and of in vitro/ex vivo corneal permeation of MAG17b of selected formulations based on polyoxyl(35)castor oil (C-EL) and polyethylene glycol (80) sorbitan monolaurate (TW80). The solubilisation of 0.5 mM MAGL17b with 3 % w/w TW80 (TW80/3-17b), through the formation of NanoMicellar structures (diameter of 12.3 nm), determined a significant permeation of MAGL17b, both through excised rabbits corneas and reconstituted corneal epithelium, with a limited corneal epithelial cells death. The blockade of MAGL activity induced a IOP reduction up to 4 mmHg in albino and pigmented rabbits after topical instillation, thus confirming the potential efficacy of the MAGL inhibition approach in the treatment of ocular pathologies.
Keywords: COR-100 EpiCorneal; In vitro/ex vivo ocular permeation; Intraocular pressure; MAGL inhibitor; Nanomicelles; Rabbit; Surfactant.
Copyright © 2022 Elsevier B.V. All rights reserved.
Conflict of interest statement
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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