Design optimization of a hyaluronic-acid based hydrogel drug-delivery device for immobilization in the eye

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Publication Type thesis
School or College College of Engineering
Department Mechanical Engineering
Author Colter, Jourdan M.
Title Design optimization of a hyaluronic-acid based hydrogel drug-delivery device for immobilization in the eye
Date 2016
Description 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, a biodegradable lm being developed by Jade Therapeutics (Salt Lake City, UT, USA), uses a proprietary, carboxymethylated, hyaluronic acid-based hydrogel (CMHA-S) to deliver drug to the ocular surface. While proven to be very safe and effective, the film tends to dislodge in the highly-lubricated eye, thereby reducing drug efficacy. In this thesis, mechanical parameters were optimized to noninvasively reduce the slip of a CMHA-S hydrogel film in the eye. Finite-element (FE) analysis was used to optimize the design of a CMHA-S for retention in the inferior fornix. Geometrical design and the effects due to friction were evaluated. Retention of the film was dependent on geometry and on the friction ratio of the film to the eyelid and globe, and 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 large, geometrical differences were negligible. Static and kinetic coefficients of friction were measured of the CMHA-S film relative to the sclera and found to be 0.18 ± 0.08 - 0.46 ± 0.13 and 0.15 ± 0.1, respectively. Effects due to sliding velocity and the addition of methylcellulose to CMHA-S were evaluated. Static coefficient of friction was significantly dependent on rate, and CMHA-S with methylcellulose was more rate dependent. Kinetic coefficient of friction was not affected by rate. CMHA-S with methylcellulose had higher friction, and was also prone to wear during the test. A second FE model was created to optimize the shape, stiffness, and thickness of a CMHA-S ocular bandage, and to evaluate the optimized shape on a range of corneal sizes. FE optimization found that a bandage shape that is molded to the cornea performs better than a bandage shape that bridges the cornea. The selected shape from this study was found to immobilize on corneal sizes that are average or smaller-than-average. Increasing elastic modulus of CMHA-S decreased relative displacement between the bandage and the cornea; however, increases from the current CMHA-S modulus minimally affected displacement. Thickness of the bandage did not greatly affect its displacement.
Type Text
Publisher University of Utah
Subject CMHA-S; Finite element analysis; Friction; Ocular drug delivery; Ophthalmology; Biomedical engineering; Mechanical engineering; Biomechanics
Dissertation Name Master of Science
Language eng
Rights Management (c) Jourdan Colter
Format Medium application/pdf
ARK ark:/87278/s6qz6jpj
Setname ir_etd
ID 1370220
Reference URL https://collections.lib.utah.edu/ark:/87278/s6qz6jpj
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