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      Targeted Drug Delivery in the Suprachoroidal Space by Swollen Hydrogel Pushing

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          Abstract

          Purpose

          The purpose is to target model drug particles to the posterior region of the suprachoroidal space (SCS) of the eye controlled via pushing by hydrogel swelling.

          Methods

          A particle formulation containing 1% hyaluronic acid (HA) with fluorescent polymer particles and a hydrogel formulation containing 4% HA were introduced in a single syringe as two layers without mixing, and injected sequentially into the SCS of the rabbit eye ex vivo and in vivo using a microneedle. Distribution of particles in the eye was determined by microscopy.

          Results

          During injection, the particle formulation was pushed toward the middle of the SCS by the viscous hydrogel formulation, but less than 12% of particles reached the posterior SCS. After injection, the particle formulation was pushed further toward the macula and optic nerve in the posterior SCS by hydrogel swelling and spreading. Heating the eye to 37°C, or injecting in vivo decreased viscosity and mechanical strength of the hydrogel, thereby allowing it to swell and flow further in the SCS. A high salt concentration (9% NaCl) in the hydrogel formulation further increased hydrogel swelling due to osmotic flow into the hydrogel. In this way, up to 76% of particles were delivered to the posterior SCS from an injection made near the limbus.

          Conclusions

          This study shows that model drug particles can be targeted to the posterior SCS by HA hydrogel swelling and pushing without particle functionalization or administering external driving forces.

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          Most cited references45

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          Adverse events and complications associated with intravitreal injection of anti-VEGF agents: a review of literature.

          Intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents is increasingly used for the treatment of a wide variety of retinal diseases, including age-related macular degeneration, diabetic retinopathy and retinal vascular occlusions, and retinopathy of prematurity. Despite encouraging results in halting the disease and improving the vision, intravitreal injection of anti-VEGF agents may be associated with systemic adverse events and devastating ocular complications. In this review, we provide an overview of safety data for intravitreal injection of common anti-VEGF agents.
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            Pharmacokinetic aspects of retinal drug delivery

            Drug delivery to the posterior eye segment is an important challenge in ophthalmology, because many diseases affect the retina and choroid leading to impaired vision or blindness. Currently, intravitreal injections are the method of choice to administer drugs to the retina, but this approach is applicable only in selected cases (e.g. anti-VEGF antibodies and soluble receptors). There are two basic approaches that can be adopted to improve retinal drug delivery: prolonged and/or retina targeted delivery of intravitreal drugs and use of other routes of drug administration, such as periocular, suprachoroidal, sub-retinal, systemic, or topical. Properties of the administration route, drug and delivery system determine the efficacy and safety of these approaches. Pharmacokinetic and pharmacodynamic factors determine the required dosing rates and doses that are needed for drug action. In addition, tolerability factors limit the use of many materials in ocular drug delivery. This review article provides a critical discussion of retinal drug delivery, particularly from the pharmacokinetic point of view. This article does not include an extensive review of drug delivery technologies, because they have already been reviewed several times recently. Instead, we aim to provide a systematic and quantitative view on the pharmacokinetic factors in drug delivery to the posterior eye segment. This review is based on the literature and unpublished data from the authors' laboratory.
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              Current and future ophthalmic drug delivery systems. A shift to the posterior segment.

              Topical eye drop administration is useful only for the treatment of anterior segment diseases. The posterior eye segment is an important therapeutic target with unmet medical needs. The leading causes of visual impairment in the industrial countries are related to the disorders in the posterior eye tissues. New drugs for the medication of the posterior ocular segment have emerged, but most drugs are delivered by repeated intravitreal injections. Effective, safe, and comfortable methods of drug delivery are needed. The emerging methods include polymeric-controlled release injections and implants, nanoparticulates, microencapsulated cells, iontophoresis, and gene medicines. The biggest drug delivery challenge is to develop effective methods for posterior segment therapies that would also be applicable for the out-patient use.
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                Author and article information

                Journal
                Invest Ophthalmol Vis Sci
                Invest. Ophthalmol. Vis. Sci
                iovs
                Invest Ophthalmol Vis Sci
                IOVS
                Investigative Ophthalmology & Visual Science
                The Association for Research in Vision and Ophthalmology
                0146-0404
                1552-5783
                April 2018
                : 59
                : 5
                : 2069-2079
                Affiliations
                [1 ]School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States
                [2 ]Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand
                Author notes
                Correspondence: Mark R. Prausnitz, School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 311 Ferst Drive NW, Atlanta, GA 30332, USA; prausnitz@ 123456gatech.edu .
                Article
                iovs-59-05-14 IOVS-17-23758R2
                10.1167/iovs.17-23758
                5909801
                29677369
                d30792ed-0c85-4422-9e84-db46e0c91672
                Copyright 2018 The Authors

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

                History
                : 3 January 2018
                : 20 March 2018
                Categories
                Retina

                hyaluronic acid,hydrogel swelling,microneedle injection,new zealand white rabbit,ocular drug delivery,posterior segment,suprachoroidal space injection

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