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Ghanashyam Acharya, Xiaoyong Yuan, Daniela Marcano, Crystal Shin, Xia Hua, Lucas Isenhart, Stephen C Pflugfelder; Nanowafer Drug Delivery to Treat Corneal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5032.
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© ARVO (1962-2015); The Authors (2016-present)
Development of a controlled release nanowafer drug delivery system for treating corneal neovascularization.
The axitinib-nanowafers (Axi-NW) were fabricated via the hydrogel template strategy with a few modifications. The nanowafers thus prepared were tested in ocular burn induced murine model. The corneas were subjected to laser scanning confocal imaging and RT-PCR analysis of gene expression.
The nanowafer is a tiny transparent circular disc containing arrays of drug loaded nanoreservoirs (Figure 1). The in vivo therapeutic efficacy of the nanowafer was demonstrated by treating corneal neovascularization (CNV) in a murine ocular burn (OB) model. In this study, once a day Axi-5-NW treatment was compared with Axi eye drops (0.1%) administered twice a day for its therapeutic effect in inhibiting CNV in OB mouse model. The Axi-5-NW treatment restricted the proliferation of blood vessels to the limbal area and treated eyes very closely resembled the healthy uninjured cornea. However, the OB controls - PVA-NW and Axi eye drop treated corneas exhibited extensive neovascularization (Figure 2a-e). In the case of Axi-5-NW treatment, the amount of drug delivered to the cornea was 5 µg per day, and for axitinib eye drop treatment it was 10 µg per day. Although, eye drop treated mice received twice the drug dosage as those treated with Axi-5-NW, still Axi-5-NW treatment was twice as efficacious as the eye drop treatment (Figure 2f). The RT-PCR study revealed that Axi-NW was very effective in downregulating the drug target genes VEGF-A, VEGF-R1, VEGF-R2, PDGFR-A, PDGFR-B, TNF-α, bFGF and TGF-β, compared to the untreated OB and Axi-eye drop treatment.
Once a day axitinib delivery by the nanowafer is more efficacious than the twice a day topical eye drop treatment.
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