June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Nanowafer Drug Delivery to Treat Corneal Neovascularization
Author Affiliations & Notes
  • Ghanashyam Acharya
    Ophthalmology, Baylor College of Medicine, Houston, TX
  • Xiaoyong Yuan
    Ophthalmology, Baylor College of Medicine, Houston, TX
  • Daniela Marcano
    Ophthalmology, Baylor College of Medicine, Houston, TX
  • Crystal Shin
    Ophthalmology, Baylor College of Medicine, Houston, TX
  • Xia Hua
    Ophthalmology, Baylor College of Medicine, Houston, TX
  • Lucas Isenhart
    Ophthalmology, Baylor College of Medicine, Houston, TX
  • Stephen C Pflugfelder
    Ophthalmology, Baylor College of Medicine, Houston, TX
  • Footnotes
    Commercial Relationships Ghanashyam Acharya, None; Xiaoyong Yuan, None; Daniela Marcano, None; Crystal Shin, None; Xia Hua, None; Lucas Isenhart, None; Stephen Pflugfelder, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 5032. doi:
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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)

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Abstract
 
Purpose
 

Development of a controlled release nanowafer drug delivery system for treating corneal neovascularization.

 
Methods
 

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.

 
Results
 

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.

 
Conclusions
 

Once a day axitinib delivery by the nanowafer is more efficacious than the twice a day topical eye drop treatment.  

 
<br /> Figure 1. Schematic of the Ocular drug delivery nanowafer instilled on the cornea.
 
<br /> Figure 1. Schematic of the Ocular drug delivery nanowafer instilled on the cornea.
 
 
Figure 2. Axitinib-nanowafer is more efficacious than the topical eye drop treatment. Confocal fluorescence images revealing the enhanced therapeutic efficacy of Axi-nanowafer. a, Healthy cornea. b, OB induced cornea. c, PVA-NW. d, Axi-NW. e, Twice a day Axi-eye drop (0.1%) treatment. f, Quantification of corneal neovascularization volume. n = 3 animals,<br /> * P<0.05 vs OB control. All error bars represent standard deviation from the mean.<br />
 
Figure 2. Axitinib-nanowafer is more efficacious than the topical eye drop treatment. Confocal fluorescence images revealing the enhanced therapeutic efficacy of Axi-nanowafer. a, Healthy cornea. b, OB induced cornea. c, PVA-NW. d, Axi-NW. e, Twice a day Axi-eye drop (0.1%) treatment. f, Quantification of corneal neovascularization volume. n = 3 animals,<br /> * P<0.05 vs OB control. All error bars represent standard deviation from the mean.<br />

 
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