A corneal-penetrating eye drop formulation for enhanced therapeutic efficacy of soft corticosteroids against anterior uveitis

Eye drop administration suffers from low bioavailability due to inadequate preocular retention and tissue penetration, which leads to multiple administration to achieve ocular therapeutic concentration. We tested the hypothesis that a cluster bomb releasing corneal-penetrating bomblet of drug assembles would increases drug bioavailability and reduce the administration frequency of corticosteroids in uveitis treatment. The microparticulate drug delivery system was obtained from host-guest assembly of (2-hydroxypropyl)-γ-cyclodextrin with loteprednol etabonate, a hydrophilic polymer, hydroxypropyl methylcellulose, and a stabilizer, caffeine, and polysorbate 80. The pharmacokinetics and pharmacodynamics studies of the proposed microparticles were performed on normal and on experimental uveitis model of New Zealand White rabbits, respectively. In comparison to the commercial microparticulate formulation Lotemax®, our formulation showed 5.4 and 3.5-fold increase of maximum drug concentration in aqueous humor and iris/ciliary body (target tissue of anterior uveitis) in vivo, respectively, while the intraocular pressure remains normal. Along with the enhanced drug exposure in target tissue, the drug dosing frequency can be reduced into half with a comparable outcome to the typical steroid treatment against autoimmune-induced uveitis by using our eye drop formulation. The microparticulate drug delivery system was developed to provide a potential solution to increase drug bioavailability in ocular tissues and with which the administration frequency could be reduced. Our results suggest that these goals could be successfully achieved by using the proposed eye drop formulation. [Display omitted]