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      Stimulus-Responsive Contact Lens for IOP Measurement or Temperature-Triggered Drug Release

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          Abstract

          Purpose

          Continuous monitoring of elevated intraocular pressure and timely drug delivery for successful treatment of glaucoma are necessary to reduce intraocular pressure (IOP), which shows wide variations across the circadian pattern and in response to medication. This in vivo study presents a new contact lens-based method of optical IOP measurement or temperature-triggered drug elution.

          Methods

          A contact lens with moiré patterns of concentric circles measures the changes in eyeball diameter of a rabbit glaucoma model due to changes in IOP by superimposing a camera-captured image onto the micro pattern of the contact lens with a computer-assisted virtual reference image. Drug elution from the nanoporous bicontinuous microemulsion contact lens (BME-CL) into the eye of the rabbit was triggered by a temperature-responsive nanogel drug carrier.

          Results

          The moiré pattern change on the contact lens was proportional to the IOP increase in the rabbit eye either ex vivo or in vivo and was also correlated with imaging-based alterations in the anterior chamber angle at a range of IOP values (3–40 mm Hg). The cumulative drug absorbed reached as high as 10.6 µg/mL aqueous humor until 7 days after wearing the BME-CL, and a 33% decrease in IOP was observed at 3 hours after drug elution.

          Conclusions

          The results suggest that continuous measurement and treatment of elevated IOP are feasible using moiré pattern-inscribed and thermosensitive drug-eluting contact lenses, respectively.

          Translational Relevance

          Pressure-sensing or thermosensitive contact lenses enable monitoring IOP or drug release triggered by body temperature for the treatment of glaucoma patients.

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          Most cited references16

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          Wearable smart sensor systems integrated on soft contact lenses for wireless ocular diagnostics

          Wearable contact lenses which can monitor physiological parameters have attracted substantial interests due to the capability of direct detection of biomarkers contained in body fluids. However, previously reported contact lens sensors can only monitor a single analyte at a time. Furthermore, such ocular contact lenses generally obstruct the field of vision of the subject. Here, we developed a multifunctional contact lens sensor that alleviates some of these limitations since it was developed on an actual ocular contact lens. It was also designed to monitor glucose within tears, as well as intraocular pressure using the resistance and capacitance of the electronic device. Furthermore, in-vivo and in-vitro tests using a live rabbit and bovine eyeball demonstrated its reliable operation. Our developed contact lens sensor can measure the glucose level in tear fluid and intraocular pressure simultaneously but yet independently based on different electrical responses.
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            Smart drug delivery systems: from fundamentals to the clinic.

            Forty years after the first reports on stimuli-responsive phase transitions in synthetic hydrogels, the first medicines based on responsive components are approaching the market. Sensitiveness to internal or external signals of the body can be achieved by means of materials (mostly polymers, but also lipids and metals) that modify their properties as a function of the intensity of the signal and that enable the transduction into changes in the delivery system that affect its ability to host/release a therapeutic substance. Integration of responsive materials into implantable depots, targetable nanocarriers and even insertable medical devices can endow them with activation-modulated and feedback-regulated control of drug release. This review offers a critical overview of therapeutically-interesting stimuli to trigger drug release and the evolution of responsive materials suitable as functional excipients, illustrated with recent examples of formulations in clinical trials or already commercially available, which can provide a perspective on the current state of the art on smart drug delivery systems.
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              In vivo performance of a drug-eluting contact lens to treat glaucoma for a month.

              For nearly half a century, contact lenses have been proposed as a means of ocular drug delivery, but achieving controlled drug release has been a significant challenge. We have developed a drug-eluting contact lens designed for prolonged delivery of latanoprost for the treatment of glaucoma, the leading cause of irreversible blindness worldwide. Latanoprost-eluting contact lenses were created by encapsulating latanoprost-poly(lactic-co-glycolic acid) films in methafilcon by ultraviolet light polymerization. In vitro and in vivo studies showed an early burst of drug release followed by sustained release for one month. Contact lenses containing thicker drug-polymer films demonstrated released a greater amount of drug after the initial burst. In vivo, single contact lenses were able to achieve, for at least one month, latanoprost concentrations in the aqueous humor that were comparable to those achieved with topical latanoprost solution, the current first-line treatment for glaucoma. The lenses appeared safe in cell culture and animal studies. This contact lens design can potentially be used as a treatment for glaucoma and as a platform for other ocular drug delivery applications.
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                Author and article information

                Journal
                Transl Vis Sci Technol
                Transl Vis Sci Technol
                tvst
                TVST
                Translational Vision Science & Technology
                The Association for Research in Vision and Ophthalmology
                2164-2591
                09 March 2020
                March 2020
                : 9
                : 4
                : 1
                Affiliations
                [1 ] Department of Optometry and Vision Science, College of Medical Science, Catholic University of Daegu , Kyungsan City, Korea
                [2 ] Department of Radiology and Biomedical Engineering, College of Medical Science, Catholic University of Daegu , Daegu, Korea
                [3 ] Department of Ophthalmology, School of Medicine, Catholic University of Daegu , Daegu, Korea
                [4 ] Center for Biomicrosystems, Korea Institute of Science and Technology , Seoul, Korea
                Author notes
                Correspondence: Jong-Ki Kim, Department of Biomedical Engineering and Radiology, School of Medicine, Catholic University of Daegu, 33 Duryugongwonro 17-gil, Daegu 42472, Korea. e-mail: jkkim@ 123456cu.ac.kr
                Ji-Yoon Kang, Korea Institute of Science and Technology, 5, Hwarang-ro 14-gil Seongbuk-gu Seoul, 02792, Seongbuk-ku, Seoul 42002, Korea. e-mail: jykang@ 123456kist.re.kr
                [*]

                S-HL and K-SS contributed equally to this article.

                Article
                TVST-19-2057
                10.1167/tvst.9.4.1
                7396181
                14e091f7-ef60-4f01-8487-12244b8ffac2
                Copyright 2020 The Authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 12 December 2019
                : 18 October 2019
                Page count
                Pages: 10
                Categories
                Article
                Article

                intraocular pressure,contact lenses,moiré pattern,drug delivery,temperature triggering

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