REVIEWS Drug Discovery Today  Volume 16, Numbers 5/6  March 2011 Drug delivery to the posterior segment of the eye Thilini Rasika Thrimawithana 1 , Simon Young 1 , Craig Robert Bunt 2 , Colin Green 3 and Raid Ghassan Alany 1,4,5 1 Drug Delivery Research Unit (DDRU), School of Pharmacy, Faculty of Medical and Health Sciences, The University of Auckland, Auckland 1010, New Zealand 2 AgResearch Limited, Christchurch 8140, New Zealand 3 Department of Ophthalmology, Faculty of Medical and Health Sciences, The University of Auckland, Auckland 1010, New Zealand 4 School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland 1010, New Zealand Delivery of drugs to the posterior eye is challenging, owing to anatomical and physiological constrains of the eye. There is an increasing need for managing rapidly progressing posterior eye diseases, such as age- related macular degeneration, diabetic retinopathy and retinitis pigmentosa. Drug delivery to the posterior segment of the eye is therefore compounded by the increasing number of new therapeutic entities (e.g. oligonucleotides, aptamers and antibodies) and the need for chronic therapy. Currently, the intravitreal route is widely used to deliver therapeutic entities to the retina. However, frequent administration of drugs via this route can lead to retinal detachment, endophthalmitis and increased intraocular pressure. Various controlled delivery systems, such as biodegradable and non-biodegradable implants, liposomes and nanoparticles, have been developed to overcome such adverse effects, with some success. The periocular route is a promising alternative, owing to the large surface area and the relatively high permeability of the sclera. Yet, the blood–retinal barrier and efflux transporters hamper the transport of therapeutic entities to the retina. As such, the efficient delivery of drugs to the posterior eye remains a major challenge facing the pharmaceutical scientist. In this review, we discuss the barriers of the posterior eye drug delivery and the various drug-delivery strategies used to overcome these barriers. Introduction Diseases of the eye vary from minor conjunctivitis to irreversible visual impairment caused mainly by diseases of the posterior eye. The most prevalent posterior eye diseases which cause visual impairment include age-related macular degeneration (AMD), macular oedema secondary to retinal vein occlusion, uveitis, diabetic retinopathy, cytomegalovirus (CMV) retinitis and retinitis pigmentosa [1]. Depending on the disease origin, ocular drug-delivery systems vary from simple topical ocular formulations to systems that require complex engineering solutions, such as intraocular implants [2,3]. Nonetheless, the tight cellular membranes of the eye and the various barriers that restrict the transport of fluids and solutes to the visual cells hinder the successful administration of therapeutic agents. As such, many novel strategies have been developed to circumvent these ocular barriers. This review pro- vides an overview of the routes of drug delivery to the posterior eye, the biological barriers to posterior eye drug delivery and the novel strategies utilized to overcome these challenges. Routes of drug delivery to the posterior eye Topical, systemic, intravitreal and periocular routes can be used to deliver pharmaceuticals to the posterior segment of the eye. The topical route is inefficient in delivering therapeutic concentrations of a drug to the posterior segment, owing to rapid drainage through the nasolacrimal ducts, low permeability of the corneal epithelium, systemic absorption and the blood–aqueous barrier. Reviews  POST SCREEN Corresponding author:. Alany, R.G. (r.alany@auckland.ac.nz), Thrimawithana, T.R. (t.thrimawithana@auckland.ac.nz) 5 Current address: School of Pharmacy and Chemistry, Kingston University London, Kingston upon Thames, UK. 270 www.drugdiscoverytoday.com 1359-6446/06/$ - see front matter ß 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.drudis.2010.12.004