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Evaluation of Pregabalin bioadhesive multilayered microemulsion IOP-lowering eye drops.

Authors :
Maria, Doaa N.
Ibrahim, Mohamed M.
Kim, Minjae J.
Maria, Sara N.
White, William A.
Wang, XiangDi
Hollingsworth, T.J.
Jablonski, Monica M.
Source :
Journal of Controlled Release. Sep2024, Vol. 373, p667-687. 21p.
Publication Year :
2024

Abstract

In spite of available treatment options, glaucoma continues to be a leading cause of irreversible blindness in the world. Current glaucoma medications have multiple limitations including: lack of sustained action; requirement for multiple dosing per day, ocular irritation and limited options for drugs with different mechanisms of action. Previously, we demonstrated that pregabalin, a drug with high affinity and selectivity for CACNA2D1, lowered IOP in a dose-dependent manner. The current study was designed to evaluate pregabalin microemulsion eye drops and to estimate its efficacy in humans using in silico methods. Molecular docking studies of pregabalin against CACNA2D1 of mouse, rabbit, and human were performed. Pregabalin microemulsion eye drops were characterized using multiple in vivo studies and its stability was evaluated over one year at different storage conditions. Molecular docking analyses and QSPR of pregabalin confirmed its suitability as a new IOP-lowering medication that functions using a new mechanism of action by binding to CACNA2D1 in all species evaluated. Because of its prolonged corneal residence time and corneal penetration enhancement, a single topical application of pregabalin ME can provide an extended IOP reduction of more than day in different animal models. Repeated daily dosing for 2 months confirms the lack of any tachyphylactic effect, which is a common drawback among marketed IOP-lowering medications. In addition, pregabalin microemulsion demonstrated good physical stability for one year, and chemical stability for 3–6 months if stored below 25 °C. Collectively, these outcomes greatly support the use of pregabalin eye drops as once daily IOP-lowering therapy for glaucoma management. [Display omitted] • Molecular docking analyses estimate strong binding affinity of pregabalin, a novel therapy for open angle glaucoma • Pregabalin microemulsion eye drops supports once daily use by extending the precorneal drug residence time up to 24 h • Pregabalin microemulsion eye drops didn't have any tachyphylactic effect upon repeated dosing for 2 months • Pregabalin microemulsion eye drops is chemically stable for 3–6 month at temperature below 25 °C. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
01683659
Volume :
373
Database :
Academic Search Index
Journal :
Journal of Controlled Release
Publication Type :
Academic Journal
Accession number :
179498504
Full Text :
https://doi.org/10.1016/j.jconrel.2024.07.061