Recent advances in ophthalmic drug delivery

Abstract

Topical ocular drug bioavailability is notoriously poor, in the order of 5% or less. This is a consequence of effective multiple barriers to drug entry, comprising nasolacrimal drainage, epithelial drug transport barriers and clearance from the vasculature in the conjunctiva. While sustained drug delivery to the back of the eye is now feasible with intravitreal implants such as Vitrasert (-6 months), Retisert (-3 years) and Iluvien (-3 years), currently there are no marketed delivery systems for long-term drug delivery to the anterior segment of the eye. The purpose of this article is to summarize the resurgence in interest to prolong and improve drug entry from topical administration. These approaches include mucoadhesives, viscous polymer vehicles, transporter-targeted prodrug design, receptor-targeted functionalized nanoparticles, iontophoresis, punctal plug and contact lens delivery systems. A few of these delivery systems might be useful in treating diseases affecting the back of the eye. Their effectiveness will be compared against intravitreal implants (upper bound of effectiveness) and trans-scleral systems (lower bound of effectiveness). Refining the animal model by incorporating the latest advances in microdialysis and imaging technology is key to expanding the knowledge central to the design, testing and evaluation of the next generation of innovative ocular drug delivery systems.

Figures

Figure 1. Permeability barriers for ocular drug delivery

Cornea and conjunctiva are key epithelial barriers encountered by topically administered drug molecules. A topically administered drug can reach the retina if it can traverse conjunctiva, sclera, choroid and the retinal pigment epithelium, in that order. Systemically administered drugs have to cross the blood–aqueous barrier to reach the intraocular tissues of the anterior segment of the eye. Systemic drugs have to cross the blood–retinal barriers, that is, the retinal pigment epithelium (outer blood–retinal barrier) or the retinal vasculature (inner blood–retinal barrier). Figure modified with permission from [128] © Taylor & Francis Group.

Figure 2. Choosing a mucoadhesive or viscous vehicle or carrier that reduces precorneal drug elimination can elevate tear fluid and aqueous humor drug levels

(A) The simulation model for prediction of ocular pharmacokinetic after topical application. (B) Simulation of tear fluid concentration of a hypothetical drug at various precorneal elimination rates. A reduction in elimination rate is anticipated with viscous or mucoadhesive vehicles. (C) Simulation of aqueous humor concentration of a hypothetical drug at various precorneal elimination rates, when other parameters are kept constant. Prior to choosing such a system, any potential blurring of the vision by the viscous vehicle should be taken into consideration.

Figure 3. Contact lenses for ocular drug delivery

Drug molecules or delivery systems can be loaded in the periphery of contact lenses by several approaches including those illustrated.

Figure 4. Punctal plug delivery systems with various components and drug-loading methods

The scheme captures a variety of technologies that are under development and is not intended to represent any one technology completely.