July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Novel Degradable Eyedrop Formulations for Treatment of Allergic Conjunctivitis
Author Affiliations & Notes
  • Mitchell Scott Ross
    Chemical Engineering, McMaster, Hamilton, Ontario, Canada
  • Talena Rambarran
    Chemical Engineering, McMaster, Hamilton, Ontario, Canada
  • Heather Sheardown
    Chemical Engineering, McMaster, Hamilton, Ontario, Canada
  • Footnotes
    Commercial Relationships   Mitchell Ross, None; Talena Rambarran, None; Heather Sheardown, None
  • Footnotes
    Support  Ontario Research Fund (C20/20: Responsive Materials for Ocular Therapy)
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 6718. doi:
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    • Get Citation

      Mitchell Scott Ross, Talena Rambarran, Heather Sheardown; Novel Degradable Eyedrop Formulations for Treatment of Allergic Conjunctivitis. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6718.

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

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Abstract

Purpose : Allergic conjunctivitis affects nearly 40% of the North American population. Topical eye drops are the most common treatment method, but it is generally accepted that less than 5% of an applied dose remains bioavailable, resulting in frequent reapplication. We tested the hypothesis that the incorporation of a chitosan crosslinker into previously developed thermo-sensitive hydrogels would yield a superior eyedrop formulation with a longer duration of action, capable of overcoming current dosing issues.

Methods : A functionalized chitosan crosslinker is synthesized using methods similar to that found in literature and characterized by nuclear magnetic resonance (NMR). The crosslinker is subsequently incorporated into the N-ispropylacrylamide (NIPAAm) based, thermo-sensitive, hydrogels previously developed by our lab for treatment of posterior eye conditions. Chitosan properties and component concentrations are optimized to yield a system with the desired thermo-gelling, mechanical, optical, biodegradable and drug releasing properties. NMR is used to visualize the various iterations of the formulation. For enzymatic degradation quantification, the hydrogels are incubated with simulated tear fluid and the dry mass of the hydrogel is measured at given time intervals. Release of ketotifen is assessed by high performance liquid chromatography (HPLC) of supernatant of incubated, loaded hydrogel samples at given time intervals.

Results : Figure 1 shows the NMR analysis of our synthesis. The functionalization of chitosan (4%) is shown to be successful from Figure 1a) to 1b) due to appearance of the peaks, labeled one and two, relating to the incorporation of a terminal acrylate group. The incorporation of the chitosan crosslinker with the hydrogel is found to be successful in Figure 1c) due to the loss of the indicated acrylate peaks. Ongoing work is focused on the release characterization and gel optimization.

Conclusions : The chitosan crosslinked NIPAAm based hydrogel has been synthesized and is being optimized to control drug release while maintaining desirable properties. This system has the ability to overcome the practical dosing issues which are seen within the stagnant allergic conjunctivitis industry. The system, while applied to allergy initially, may be used to treat other anterior conditions.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

Figure 1: a) Commercial chitosan b) Functionalized chitosan c) Chitosan crosslinked NIPAAm hydrogel

Figure 1: a) Commercial chitosan b) Functionalized chitosan c) Chitosan crosslinked NIPAAm hydrogel

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