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Jourdan Colter, Nathaniel Cady, Hee-Kyoung Lee, Brenda Mann, Barbara M Wirostko, Brittany Coats; Design optimization to improve retention of a carboxymethylated hyaluronic acid (CMHA-S) drug-delivery device. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1127.
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© ARVO (1962-2015); The Authors (2016-present)
Novel polymer, CMHA-S (Jade Therapeutics, SLC) is emerging as a controlled and localized means for drug-delivery in the treatment of ophthalmic conditions. Retention of CMHA-S films in the ocular environment is poor due to the high lubricating properties of hyaluronic acid. In this study, we used 3D finite element (FE) modeling to determine surface friction ratios that minimize displacement of the CMHA-S from the inferior fornix, and evaluated multiple geometrical designs for retention. In vivo studies validated model retention predictions.
A 3D FE model of the adult human eye, inferior fornix, and CMHA-S film was created based on anatomical dimensions and material properties in the literature. A sursumduction was applied and displacement of the film relative to the globe was measured. The optimal friction ratio between the CMHA-S film and the globe/lid was found by iteratively sweeping through coefficients of friction on each side of the hydrogel (μlid, μglobe). Eight different CMHA-S film geometries varying in size and cross-section were then evaluated in the model. The best performing geometry in the simulations was tested in New Zealand White Rabbits (N=6) for 8 days.
The optimal ratio of friction between the film and the globe/lid during normal eye movement was characterized by a linear relationship (μlid=1.40μglobe+0.07), with best retention resulting from μlid ≥ 1.4 times μglobe. This correlated with the geometry evaluation studies which found that geometries with equal or less contact area on the lid side have large displacements from the eye. The geometry with the best retention was semicircular with the curved portion facing the globe and the flat surface against the lid. The results of the in vivo study replicated the results of the FE analysis. All geometry specimens with equal contact area to the globe and lid dislodged after 1-2 days. Two out of three of the semicircular specimens lasted the full week.
FE analysis is a powerful tool that can optimize drug delivery systems for better interaction with the eye. Jade’s novel CMHA-S film is a viable topical ophthalmic drug delivery device if the 1.4:1 ratio of frictional properties against the surface of the lid and globe is maintained. This variance can be achieved through surface modifications of the hydrogel or using geometrical features to create larger frictional forces against the lid.
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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