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Kenji Kashiwagi, Hiroki Haniuda, Shinji Takeoka; Development Of Latanoprost-binding Biodegradable Nanosheet As A New Drug Delivery System For Glaucoma. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5017.
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We investigated the intraocular pressure (IOP) reducing ability and safety of latanoprost-binding bio-nanosheet (LBNS) as a new anti-glaucoma drug delivery system (DDS).
We assembled multilayered bio-nanosheet composed of chitosan sheet and sodium alginate sheet using a layer-by-layer method. Polyvinyl alcohol was casted on the bio-nanosheet for supporting bio-nanosheet to be a self-standing and latanoprost isopropyl ester was stored in the bio-nanosheet to prepare LBNS. Concentrations of latanoprost in LBNS were 25 μg/cm2, 2.5 μg/cm2, and 0.25 μg/cm2, and the thickness of LBNS was approximately 200 nm. LBNS was placed on the rat’s cornea and IOP reduction and amount of latanoprost in the aqueous humor were investigated. Local adverse effects were also confirmed by histological observation and scratch movement study.
All concentrations of LBNS significantly reduced IOP and the maximum IOP reduction was not significantly different among them at 1 day after application. 0.25 μg/cm2 LBNS showed a significant IOP reduction for one day after application only, while 2.5 μg/cm2 and 25 μg/cm2 LBNS significantly reduced IOP for seven days after application. There was no significant difference in IOP reduction between 25μg/cm2 and 2.5 μg/cm2 LBNS throughout the experiment. IOP reduction rates of 2.5 μg/cm2 LNBS 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. Latanoprost in the aqueous humor was detected up to seven days after application. Although 25 μg/cm2 LBNS showed transient hyperemia, other concentrations showed any topical adverse effect throughout the experiment. No significant difference in eye scratching movement was observed between experimented eyes ant control eyes.
A single application of LBNS on the cornea significantly reduced IOP up to seven days without severe local complications. LBNS may be a good candidate as a new anti-glaucoma DDS.
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