A Nonionic Surfactant/Chitosan Micelle System in an Innovative Eye Drop Formulation

Micelle systems composed of the polyoxyethylated nonionic surfactant Pluronic® F127 (F127) and cationic polyelectrolyte chitosan (CH) were prepared with dexamethasone (DEX) as a hydrophobic model drug. The F127/CH micelles were characterised by their hydrodynamic diameter and a zeta-potential ranging between 25.4 and 28.9 nm and + 9.3 and + 17.6 mV, respectively. The DEX loading was between 0.48% and 0.56%, and no significant influence of CH on DEX loading was observed. All micelle systems were characterised by prolonged release profiles. The addition of CH significantly enhanced the in vitro DEX release rate and transport across Caco-2 cell monolayers, as compared to the CH-free F127 micelle system. This colloidal carrier was well tolerated in rabbit eyes, and no clinically abnormal signs in various ocular structures were observed. The increase in intraocular pressure (IOP) in rabbits was used to evaluate DEX ocular bioavailability. The AUC values showed a 1.7- and 2.4-fold increase in bioavailability with F127 and F127/0.015 (w/v) % CH micelle systems, respectively, as compared to a standard DEX suspension. These data indicate improved intraocular DEX absorption from the micelle systems, which can be ascribed to both F127 and CH corneal permeability enhancement.