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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. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
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.
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.
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.
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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