Permeation dynamics of organic moiety-tuned organosilica nanoparticles across porcine corneal barriers: experimental and mass transfer analysis for glaucoma drug delivery.

Abstract

Elevated intraocular pressure is a key pathogenic factor in glaucoma, often leading to irreversible vision loss. In previous studies, we developed a novel hollow mesoporous organosilica nanocarrier functionalized with manganese(III) tetrakis(1-methyl-4-pyridyl)porphyrin (HMMN), demonstrating superior efficacy in treating primary open-angle glaucoma. This study presents a comparative analysis of the transcorneal permeability of HMMNs modified with thioether, biphenyl, and thioether/phenylene moieties in the porcine eye. Transcorneal permeability was evaluated using fluorescence intensity measurements in the porcine aqueous humor, followed by the calculation of diffusion and apparent permeability coefficients (Papp). Results reveal that thioether-modified HMMN exhibits significantly enhanced corneal permeability compared to biphenyl and thioether/phenylene-modified variants, with a diffusion coefficient of 4.88 × 10^-6cm²s^-1and a Papp of 1.30 × 10^-5cm s^-1in the porcine eye. These findings provide valuable insights into the permeability properties of hollow mesoporous organosilica nanocarriers, positioning them for broader applications in the treatment of various ocular diseases and potentially beyond. Furthermore, this work serves as a valuable reference for future studies exploring the potential of hybridized hollow mesoporous organosilica nanoparticles functionalized with diverse organic moieties for enhanced therapeutic outcomes.