Development of Latanoprost-Loaded Biodegradable Nanosheet as a New Drug Delivery System for Glaucoma

PURPOSE. We investigated the IOP reduction and safety of latanoprost-loaded biodegradable nanosheet (LBNS) as a new antiglaucoma drug delivery system (DDS). METHODS. We fabricated a 40 nm thick multilayered biodegradable nanosheet that is composed of chitosan and sodium alginate by means of the layer-by-layer method. Latanoprost isopropyl ester was loaded on the nanosheet to prepare 25, 2.5, and 0.25 mu g/cm(2) LBNSs. A nanosheet without latanoprost isopropyl ester (NS) and 0.005% latanoprost ophthalmic solution were prepared as controls. LBNSs or NS was applied to rat cornea, and IOP was monitored for 9 days. Local adverse effects and eye scratching movement also were investigated. The amount of latanoprost acid in aqueous humor and was measured in rabbits. RESULTS. The 0.25 mu g/cm(2) LBNS and 0.005% latanoprost ophthalmic solution showed significant IOP reduction only for 1 day after application, whereas the IOP reduction rates of 2.5 mu g/cm(2) LBNS at 1, 2, 4, 7, and 9 days after application were -27.0% +/- 14.8%, -22.0% +/- 16.7%, -25.8% +/- 18.0%, -22.7% +/- 20.9%, and -6.6% +/- 17.0%, respectively. The 25 mu g/cm(2) LBNS reduced IOP in a similar manner. The 25 mu g/cm(2) LBNS induced transient hyperemia, whereas the 0.25 and 2.5 mu g/cm(2) LBNSs did not exert any local adverse effects. The eye scratching movement test showed that application of 25 mu g/cm(2) LBNS did not cause any irritation of the eye. Latanoprost acid was detected in aqueous humor up to 6 days after application of 2.5 mu g/cm(2) LBNS. CONCLUSIONS. LBNS may be used as a novel antiglaucoma DDS.