Hyaluronic Acid-Based Micelles as Ocular Platform to Modulate the Loading, Release, and Corneal Permeation of Corticosteroids

The aim of this work is to prepare hyaluronic acid-based micelles as a platform to load corticosteroid drugs and to improve their corneal permeation after administration on the ocular surface. Three amphiphilic derivatives of hyaluronic acid (HA) are synthesized using different amounts of hexadecylamine (C-16-NH2). HAC(16)a, HAC(16)b, and HAC(16)c derivatives are able to form micelles by the cosolvent evaporation method and to entrap corticosteroids (dexamethasone, triamcinolone, triamcinolone acetonide). HAC(16)a and HAC(16)b micelles show the best results in terms of drug loading and particle size. They are also able to improve drug release compared to free drug solution or suspension. In addition, HAC(16)b micelles show an optimal mucoadhesion and compatibility with human corneal epithelial cells. In vitro and ex vivo permeation studies of drug-loaded HAC(16)b micelles are performed to understand the ability of these micelles to act as penetration and/or permeation enhancers.