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Finite Element Design Optimization of a Hyaluronic Acid-Based Hydrogel Drug Delivery Device for Improved Retention

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Abstract

Drug-loaded hydrogel devices are emerging as an effective means of localized and sustained drug delivery for the treatment of corneal conditions and injuries. One such device uses a novel, thiolated crosslinked carboxymethylated, hyaluronic acid-based hydrogel (CMHA-S) film to deliver drug to the ocular surface upon placement into the inferior fornix of the eye. While proven to be very safe and effective, the CMHA-S film tends to dislodge in the highly-lubricated ocular environment, thereby reducing drug delivery efficiency and drug efficacy. In this study, we used a three-dimensional computational finite element model of the eye to determine the effect of geometry and surface friction on film retention in the inferior fornix, and to evaluate multiple geometrical film designs. Retention of the film was dependent on geometry and on the friction ratio of the film to the eyelid and globe. These effects were interactive. When the ratio of friction on the lid side to the globe side of the film was low, geometry played a large role in the film’s displacement. When this ratio was high, differences in displacement due to geometry were negligible. The optimal relationship of friction between the film and its eyelid-side and globe-side surfaces was found to be linear with at least 1.4 times greater friction required on the eyelid-side for immobilization. A geometry similar to a half cylinder was found to be most effective with this friction ratio in retaining the film in the inferior fornix and in contact with the globe. Other geometries will likely require other friction ratios. In summary, CMHA-S film retention can be achieved through simple modifications of geometry and manipulation of surface interaction with the eye.

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Acknowledgments

This material is based upon work supported by the National Science Foundation under Award Number IIP-1430921, and the Department of Defense under Award Number W81XWH-14-C-0025. Any opinions, findings, and conclusions or recommendations expressed in this abstract are those of the authors and do not necessarily reflect the views of the National Science Foundation or the Department of Defense.

Disclosures

Dr. Barbara Wirostko co-founded Jade Therapeutics Inc. and holds intellectual property relating to the use of the polymer. Additionally, she discloses a financial relationship with EyeGate Pharmaceuticals Inc. in the form of employment and stock ownership. The remaining authors have no conflicts of interest to disclose.

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Authors and Affiliations

  1. Department of Mechanical Engineering, University of Utah, Mechanical Engineering Kennecott Building, 1495 E 100 South, Rm. 1550, Salt Lake City, UT, 84112, USA

    Jourdan Colter & Brittany Coats

  2. Jade Therapeutics Inc. (A wholly owned subsidiary of EyeGate Pharmaceuticals Inc.), EyeGate Pharma, 391 Chipeta Way, Suite H, Salt Lake City, UT, 84108, USA

    Barbara Wirostko

  3. Department of Ophthalmology, Moran Eye Center, University of Utah, 65 Mario Capecchi Dr., Salt Lake City, UT, 84132, USA

    Barbara Wirostko

Authors
  1. Jourdan Colter
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  2. Barbara Wirostko
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  3. Brittany Coats
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Correspondence to Brittany Coats.

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Associate Editor Joel D. Stitzel oversaw the review of this article.

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Colter, J., Wirostko, B. & Coats, B. Finite Element Design Optimization of a Hyaluronic Acid-Based Hydrogel Drug Delivery Device for Improved Retention. Ann Biomed Eng 46, 211–221 (2018). https://doi.org/10.1007/s10439-017-1962-x

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  • DOI: https://doi.org/10.1007/s10439-017-1962-x

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