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      • Article: found

      Transport Barriers in Transscleral Drug Delivery for Retinal Diseases

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          Abstract

          Transscleral delivery has emerged as an attractive method for treating retinal disorders because it offers localized delivery of drugs as a less invasive method compared to intravitreal administration. Numerous novel transscleral drug delivery systems ranging from microparticles to implants have been reported. However, transscleral delivery is currently not as clinically effective as intravitreal delivery in the treatment of retinal diseases. Transscleral drug delivery systems require drugs to permeate through several layers of ocular tissue (sclera, Bruch’s membrane-choroid, retinal pigment epithelium) to reach the neuroretina. As a result, a steep drug concentration gradient from the sclera to the retina is established, and very low concentrations of drug are detected in the retina. This steep gradient is created by the barriers to transport that hinder drug molecules from successfully reaching the retina. A review of the literature reveals 3 types of barriers hindering transscleral drug delivery: static, dynamic and metabolic. While static barriers have been examined in detail, the literature on dynamic and metabolic barriers is lacking. These barriers must be investigated further to gain a more complete understanding of the transport barriers involved in transscleral drug delivery.

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          Permeability of cornea, sclera, and conjunctiva: a literature analysis for drug delivery to the eye.

          Michael J. Noonan, John M. Prausnitz (1998)
          The objective of this study was to collect a comprehensive database of ocular tissue permeability measurements found in a review of the literature to guide models for drug transport in the eye. Well over 300 permeability measurements of cornea, sclera, and conjunctiva, as well as corneal epithelium, stroma, and endothelium, were obtained for almost 150 different compounds from more than 40 different studies. In agreement with previous work, the corneal epithelium was shown generally to control transcorneal transport, where corneal stroma and endothelium contribute significantly only to the barrier for small, lipophilic compounds. In addition, other quantitative comparisons between ocular tissues are presented. This study provides an extensive database of ocular tissue permeabilities, which should be useful for future development and validation of models to predict rates of drug delivery to the eye.
          Article 0 comments Cited 95 times – based on 0 reviews     Review now
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            Topical and systemic drug delivery to the posterior segments.

            Dennis P M Hughes, Joan Chang, O Olejnik … (2005)
            The posterior segments of the eye are exquisitely protected from the external environment. This poses unique and fairly challenging hurdles for drug delivery. It is somewhat dogmatic that topical ocular delivery is insufficient to achieve therapeutic drug levels in the posterior segments. However, some drugs are currently challenging this dogma. In this review we investigate the constraints and challenges of drug delivery to the posterior segment. Additionally, we outline several potential absorption pathways that may potentially be exploited to deliver drug to the back of the eye. Data on several compounds that achieve therapeutic posterior segment concentrations after topical dosing is presented. Finally, the issues surrounding systemic delivery to the posterior segment are reviewed.
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              Drug transport in corneal epithelium and blood-retina barrier: emerging role of transporters in ocular pharmacokinetics.

              Arto Urtti, Kati-Sisko Vellonen, Eliisa Mannermaa (2006)
              Corneal epithelium and blood-retina barrier (i.e. retinal capillaries and retinal pigment epithelium (RPE)) are the key membranes that regulate the access of xenobiotics into the ocular tissues. Corneal epithelium limits drug absorption from the lacrimal fluid into the anterior chamber after eyedrop administration, whereas blood-retina barrier restricts the entry of drugs from systemic circulation to the posterior eye segment. Like in general pharmacokinetics, the role of transporters has been considered to be quite limited as compared to the passive diffusion of drugs across the membranes. As the functional role of transporters is being revealed it has become evident that the transporters are widely important in pharmacokinetics. This review updates the current knowledge about the transporters in the corneal epithelium and blood-retina barrier and demonstrates that the information is far from complete. We also show that quite many ocular drugs are known to interact with transporters, but the studies about the expression and function of those transporters in the eye are still sparse. Therefore, the transporters probably have greater role in ocular pharmacokinetics than we currently realise.
              Article 0 comments Cited 57 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (publisher-id): ORE
                Journal ID (nlm-ta): Ophthalmic Res
                Journal ID (doi): 10.1159/issn.0030-3747
                Title: Ophthalmic Research
                Publisher: S. Karger AG
                ISSN (Print): 0030-3747
                ISSN (Electronic): 1423-0259
                Publication date Subscription-year: 2007
                Publication date (Print): October 2007
                Publication date (Electronic): 12 September 2007
                Volume: 39
                Issue: 5
                Pages: 244-254
                Affiliations
                aDepartment of Chemical and Biomolecular Engineering, University of Maryland, College Park, Md., bNational Institute of Biomedical Imaging and Bioengineering, and cNational Eye Institute, National Institutes of Health, Bethesda, Md., USA
                Article
                Publisher ID: 108117 Other ID: Ophthalmic Res 2007;39:244–254
                DOI: 10.1159/000108117
                PubMed ID: 17851264
                SO-VID: 32159731-c2e4-474e-ae5f-884cc562148c
                Copyright © © 2007 S. Karger AG, Basel
                License:

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Date received : 09 March 2007
                Date accepted : 12 June 2007
                Page count
                Figures: 3, Tables: 1, References: 124, Pages: 11
                Categories
                Subject: Review

                ScienceOpen disciplines: Vision sciences,Ophthalmology & Optometry,Pathology
                Keywords: Retina,Drug delivery,Clearance,Metabolism,Transscleral,Pharmacokinetics,Drug transport
                Data availability:
                ScienceOpen disciplines: Vision sciences, Ophthalmology & Optometry, Pathology
                Keywords: Retina, Drug delivery, Clearance, Metabolism, Transscleral, Pharmacokinetics, Drug transport

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