June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Nanowafer Drug Delivery for Restoration of Healthy Ocular Surface in Dry Eye Condition
Author Affiliations & Notes
  • Crystal Shin
    Ophthalmology, Baylor College of Medicine, Houston, TX
  • Daniela Marcano
    Ophthalmology, Baylor College of Medicine, Houston, TX
  • Johanna Henriksson
    Ophthalmology, Baylor College of Medicine, Houston, TX
  • Ghanashyam Acharya
    Ophthalmology, Baylor College of Medicine, Houston, TX
  • Stephen C Pflugfelder
    Ophthalmology, Baylor College of Medicine, Houston, TX
  • Footnotes
    Commercial Relationships Crystal Shin, None; Daniela Marcano, None; Johanna Henriksson, None; Ghanashyam Acharya, None; Stephen Pflugfelder, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 321. doi:
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      Crystal Shin, Daniela Marcano, Johanna Henriksson, Ghanashyam Acharya, Stephen C Pflugfelder; Nanowafer Drug Delivery for Restoration of Healthy Ocular Surface in Dry Eye Condition. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):321.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose
 

Dry eye is a steroid responsive ocular surface inflammatory disease. Therapeutic efficacy of dexamethasone treatment with a controlled release nanowafer (Dex-NW) or drops was compared in a murine desiccating stress model of dry eye.

 
Methods
 

Carboxymethyl cellulose (CMC) nanowafers and phospho dexamethasone loaded CMC nanowafers (Dex-NW) were fabricated by hydrogel template strategy. The in vivo efficacy of the Dex-NW was evaluated in the experimental dry eye induced mouse model by measuring corneal barrier function to 70kDa Oregon green dextran (OGD) and expression of inflammatory genes by RT-PCR.

 
Results
 

The nanowafer drug delivery system was designed for sustained controlled delivery of dexamethasone to ocular surface tissues (cornea/conjunctiva) in a controlled fashion and in vivo efficacy was demonstrated in a 5-day experimental dry eye induced mouse model. Corneal epithelial barrier disruption was measured by intensity of staining with fluorescent Oregon green conjugated dextran (OGD). Dex-NW placed on the bulbar conjunctiva on days 1 and 3 was equally effective as dexamethasone drops instilled twice a day eye for five days (Figure 1). RT-PCR analysis revealed that the down regulation of drug target genes IL-1α, IL-1β, TNF-α, IFN-δ, and MMP-3, and MMP-9 by Dex-NW treatment was comparable to twice a day topically administrated dexamethasone eye drop formulation (Figure 2). In both these studies, the dexamethasone delivered by the eye drop treatment was 20 µg compared to 5 µg of the drug delivered by the nanowafer during the same treatment period.

 
Conclusions
 

The Dex-NW was equally effective in suppressing dry eye induced corneal inflammation as conventional dexamethasone eye drops, even at a 4-fold lower drug concentration and alternate day dosing frequency.  

 
Figure 1. Corneal barrier function measurement with green fluorescent OGD staining. (a) Healthy untreated eye, (b) 5 day exposure to desiccating stress, (c), CMC drops, (d), CMC+Dex drops, (e), CMC wafers, (f) Dex-NW.
 
Figure 1. Corneal barrier function measurement with green fluorescent OGD staining. (a) Healthy untreated eye, (b) 5 day exposure to desiccating stress, (c), CMC drops, (d), CMC+Dex drops, (e), CMC wafers, (f) Dex-NW.
 
 
Figure 2. RT-PCR analysis showing that downregulation of drug target genes by Dex-NW is comparable to that of twice a day topical dexamethasone eye drop treatment.
 
Figure 2. RT-PCR analysis showing that downregulation of drug target genes by Dex-NW is comparable to that of twice a day topical dexamethasone eye drop treatment.

 
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