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

Abstract

Citation: Kashiwagi K, Ito K, Haniuda H, Ohtsubo S, Takeoka S. Development of latanoprost-loaded biodegradable nanosheet as a new drug delivery system for glaucoma. Invest Ophthalmol Vis Sci. 2013;54:5629-5637. DOI:10.1167/iovs.12-9513 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 lg/ 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 lg/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 lg/cm 2 LBNS at 1, 2, 4, 7, and 9 days after application were À27.0% 6 14.8%, À22.0% 6 16.7%, À25.8% 6 18.0%, À22.7% 6 20.9%, and À6.6% 6 17.0%, respectively. The 25 lg/cm 2 LBNS reduced IOP in a similar manner. The 25 lg/cm 2 LBNS induced transient hyperemia, whereas the 0.25 and 2.5 lg/cm 2 LBNSs did not exert any local adverse effects. The eye scratching movement test showed that application of 25 lg/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 lg/cm 2 LBNS.CONCLUSIONS. LBNS may be used as a novel antiglaucoma DDS.

Risk factors for early onset elevated intraocular pressure after pterygium surgery

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Quantitative Nanomechanical Properties of Multilayer Films Made of Polysaccharides through Spray Assisted Layer-by-Layer Assembly

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Sustained Delivery of Timolol Maleate for Over 90 Days by Subconjunctival Injection

“…Several formulations of latanoprost, including biodegradable nanosheets with sustained delivery up to 1 month, have been reported. [49][50][51] Recently, a subconjunctival injection of latanoprost-loaded egg phosphatidylcholine liposomes showed sustained IOP reduction for 120 days in a primate model of glaucoma. 52 A pilot study of this approach involving 6 human subjects has recently been conducted in Singapore.…”