Transport Barriers in Transscleral Drug Delivery for Retinal Diseases

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.

A study of the dexamethasone sodium phosphate release properties from a periocular capsular drug delivery system

“…and the dynamic clearance mechanisms (subconjunctivalepiscleral blood/lymph vessel flow for 80% and choriocapillaris blood flow for 20%) (Robinson et al, 2006). The drugs have to permeate several layers (sclera, choroids-Bruch's membrane and retinal pigment epithelium) to reach the neuroretina (Kim et al, 2007). The transscleral intraocular tissue distribution of corticosteroids was primarily driven by the drug solubility (Thakur et al, 2011).…”

Lipid Nanoparticles for Ocular Drug Delivery

“…Intraocular (intravitreal or intraretinal) drug delivery is the most invasive route, in that it contains penetrating the eyeball and thus is not free of injection-related complications. Thus, compared with the other drug delivery routes, it reaches the highest bioavailability in posterior tissues [29,30] . However, this route causes to undesirable of a solid lipid, where the drug is normally incorporated, with an average diameter below 1 µm [44,45] .…”

Basic Research and Clinical Application of Drug Delivery Systems for the Treatment of Age-Related Macular Degeneration

“…The reason for such zones or contours of steady state concentration is not necessarily diffusion limitation, but rather the presence of continuous dynamic clearance mechanisms in the posterior segment. There are two main mechanisms of drug clearance for intravitreally administered drugs in the eye: the anterior elimination pathway via counterdirectional bulk aqueous flow and the posterior elimination pathway via vitreoretinochoroidal bulk flow due to hydrostatic and osmotic pressure gradients in the inner, middle, and outer coats of the posterior segment (Kim, Lutz, Wang, et al 2007). An additional mechanism to consider is the transcellular carrier-mediated transporters found on the RPE.…”