September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
An eye drop with enhanced hyaluronic acid (HA) retention and delivery
Author Affiliations & Notes
  • Anirudha Singh
    Johns Hopkins, Baltimore, Maryland, United States
  • David Lee
    Johns Hopkins, Baltimore, Maryland, United States
  • Qiaozhi Lu
    Johns Hopkins, Baltimore, Maryland, United States
  • Jennifer Elisseeff
    Johns Hopkins, Baltimore, Maryland, United States
  • Footnotes
    Commercial Relationships   Anirudha Singh, None; David Lee, None; Qiaozhi Lu, None; Jennifer Elisseeff, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 418. doi:
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      Anirudha Singh, David Lee, Qiaozhi Lu, Jennifer Elisseeff; An eye drop with enhanced hyaluronic acid (HA) retention and delivery. Invest. Ophthalmol. Vis. Sci. 2016;57(12):418.

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

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Abstract

Purpose : HA wetting solutions effectively lubricate the ocular surface and are used clinically for corneal epithelial wound healing and to treat dry eye disorders. However, HA has a low eye residence time owing to limited adhesion, which necessitates frequent instillation of HA-based eye drops. Conversely, more viscous artificial tears are known to blur vision and interfere with blinking. We therefore developed an eye drop formulation based on a HA binding polymer-peptide system that binds and retains HA, from tear fluid or exogenous application, for longer periods of time at the surface of the eye through transmembrane mucins or collagen.

Methods : Rabbit conjunctival tissue was targeted to test the binding ability of multiple peptides by a 4'-hydroxyazobenzene-2-carboxylic acid assay. We further performed overtime HA release studies on peptide treated samples by measuring fluorescence values with full area scan periodically every 5 minutes for a total of 25 minutes and also 2, 4 and 16 hours after the initial fluorescence measurement. The value of fluorescence was compared to positive and negative controls. All groups were performed in triplicate. One-way ANOVA was performed among groups to determine any statistically significance in mean values of HA retention on ex vivo rabbit ocular tissues (p ≤ 0.05 was considered statistically significant). In vivo studies were performed on mice treated with an HA eye drop solution containing the polymer-peptide system (total 5 μl) by combining a 1:1 volume ratio of polymer-peptide (5 mg/ml) and HA (1 mg/ml) and imaged using a fluorescent dissecting microscope, allowing us to take images of the eye overtime without harvesting the tissues.

Results : Our results showed that in an ex vivo rabbit eye model (normal), the HA and mucin binding polymer-peptide eye drop solution bound HA 1.8 times more in the beginning, 1.6 times more after 25 min and 1.2 times more even at 24 h compared to an HA-only eye drop (p<0.05 at each data point). Similarly, in an in vivo mouse model (normal), HA immobilized through the peptide was observed even after 15 min compared to 5 min for the control HA that was not bound with the peptide.

Conclusions : HABpep eye drop solution prolonged HA retention at the ocular surface in both ex vivo and in vivo animal models (normal); however, its efficacy has to be tested in treating a dry eye model, where transmembrane mucins are compromised.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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