Enhanced ocular delivery of brinzolamide via β-cyclodextrin-based micelles for glaucoma management

Brinzolamide (BRZ) is a carbonic anhydrase inhibitor for primary open-angle glaucoma (POAG) and ocular hypertension (OH). However, it suffers from poor aqueous solubility, leading to irritation and reduced patient compliance. This study introduces a novel β-cyclodextrin (β-CD)-based micellar formulation (MCLs) to improve solubility, safety, and therapeutic performance. BRZ micellar formulations (BRZ-MCLs) were developed using Pluronic F68/F127 and β-CD to enhance solubility. Characterization included particle size, polydispersity index (PDI), entrapment efficiency (EE%), and in vitro release. Irritation was assessed via HET-CAM (Hen's Egg Chorioallantoic Membrane) and Draize tests. Molecular docking (PDB ID: 4M2R) and TOPKAT predicted stable binding and favorable safety. The optimized BRZ-MCLs showed a particle size of 80 ± 7.7 nm, low PDI (0.145 ± 0.06), negative ZP (- 11.8 ± 0.21), and high EE% (81.95 ± 1.62%). They achieved sustained drug release (85 ± 0.275% over 72 h), significantly higher than the BRZ suspension (69 ± 0.202%). Molecular docking indicated stable BRZ binding with THR A: 200, PHE A:131, and PRO A:202. Toxicity assessments confirmed BRZ-MCLs were non-irritating (irritation score (IS) = 0) and non-mutagenic. This β-CD micellar system offers a novel, patient-friendly strategy for ocular BRZ delivery, addressing solubility and irritation issues while enhancing therapeutic outcomes in glaucoma management.