Roles of the conjunctiva in ocular drug delivery: a review of conjunctival transport mechanisms and their regulation

Conjunctiva plays many roles including protection of ocular surface, production of tear film, and a conduit for drug clearance (depending on drug properties) into the systemic circulation or for drug transport to the deep tissues of the eye. The conjunctiva, which is a moderately tight epithelium, endowed with various transport processes for the homeostasis of ions, solutes, and water in the conjunctival surface and tear film. Modulation of ion transport in the conjunctiva leads to alterations in transconjunctival fluid flow that may become useful for treatment of dry-eye state in the eye. As a possible drug delivery route to the posterior portion of the eye, conjunctiva is an attractive route due to both larger surface area than that of cornea and expression of several key transport processes. Tear contains D-glucose and many amino acids, in addition to the usual ions in the body fluids. Several ion-coupled solute transport processes for absorption of amino acids, D-glucose, monocarboxylate, nucleosides, and dipeptides are expressed in the conjunctiva. Thanks to the rich endowment of these transport processes, drug transport across the conjunctiva into the intraocular tissues may become quite feasible. Subconjunctival injection of microparticles and matrix materials (which allows sustained release of drugs) is shown to maintain reasonable levels of various drugs in the vitreous, perhaps attesting to the fact that conjunctiva per se may contribute as a part of multiple transport barrier(s) in ocular drug delivery. In addition, several conjunctival approaches have been investigated to optimize treatment of dry-eye syndrome and intraocular diseases, and more can be accomplished in the coming years. (c) 2005 Elsevier B.V. All rights reserved.