A nanoparticle-based ophthalmic formulation of dexamethasone enhances corneal permeability of the drug and prolongs its corneal residence time

We designed ophthalmic formulations containing dexamethasone-loaded solid nanoparticles (DEX_nano dispersion), and investigated corneal permeability and toxicity. 0.1% dexamethasone (DEX) powder (DEX microparticles), 0.026% methyl p-hydroxybenzoate (MP), 0.014% propyl p-hydroxybenzoate (PP), and 0.5% methylcellulose were used, and the DEX_nano dispersion was prepared by the bead mill method. The mean particle size of DEX_nano dispersion was 78 nm. Antimicrobial activity of the DEX_nano dispersion were measured by using Escherichia coli, and the corneal epithelium-debrided rat model and HCE-T cells (immortalized human corneal epithelial cell line) were used to estimate the corneal toxicity. The transcorneal penetration of the DEX_nano dispersion were evaluated in the corneas of rabbit. The DEX_nano dispersion was found to be highly stable until 14 d after its preparation. Although DEX itself did not exhibit antimicrobial activity, the DEX_nano dispersion containing parabens (MP and PP) showed high antimicrobial activity, approximately equal to that of the solution containing parabens without DEX. The corneal penetration rate (J_c) and mean residence time (MRT) of DEX from the DEX_nano dispersion were approximately 5.1- and 1.3-fold higher, respectively, than those of a dispersion containing DEX microparticles (mean particle size, 11.3 µm). In addition, no significant difference was found in corneal stimulation between the vehicle and DEX_nano dispersion. In conclusion, we successfully prepared high quality dispersion containing DEX solid nanoparticles, and the nanoparticle-based ophthalmic formulation of DEX enhanced the corneal permeability and residence time of the drug. It is possible that DEX_nano dispersion will show increased effectiveness in treating ocular inflammation.