Drug Transport by the Blood-Aqueous Humor Barrier of the Eye

Abstract

The ocular barriers (cornea, blood-retinal barrier, and blood-aqueous humor barrier) make treating eye diseases with therapeutic drugs challenging. The tight capillary endothelium of the iris and the ciliary body epithelium form the blood-aqueous humor barrier. The iris and ciliary body (iris-ciliary body) express a variety of drug transporters in the ATP-binding cassette and solute carrier (SLC) families. ATPbinding cassette family drug transporters that are present in the irisciliary body include P-glycoprotein, breast cancer resistance protein, and several multidrug resistance-associated proteins. SLC family drug transporters that are present in the iris-ciliary body include organic anion transporters, organic anion transporting polypeptides, bile acid transporters (apical sodium-dependent bile salt transporter and sodium taurocholate cotransporter), organic cation transporters (novel organic cation transporter and multidrug and toxin extrusion transporter) and peptide transporters. Freshly dissected iris-ciliary body preparations actively accumulate a variety of substrates of SLC drug transporters that are expressed in the tissue. The ciliary body in vitro supports active transport in the aqueous humor-to-blood direction of several substrates of organic anion transporters and multidrug resistance-associated proteins, consistent with the subcellular localization of these transporters in the ciliary body epithelium. In vivo data suggest that drug transporters in the iris-ciliary body reduce the permeation of drugs in the direction of blood-toaqueous humor, thereby reducing ocular drug bioavailability, and are also involved in active drug elimination from the aqueous humor. An understanding of the influence on pharmacokinetics of drug transporters in the blood-aqueous humor barrier should help improve drug delivery and efficacy in the eye.

Polymeric micelles for ocular drug delivery: From structural frameworks to recent preclinical studies

“…However, the BAB is not considered a complete barrier because of the fenestrated capillaries present in the ciliary body stroma. These fenestrated vessels being the secondary source of plasma protein leakage to the iris also allow passage of small molecules to enter the iridial circulation [31]. The blood-retinal barrier (BRB) present in the posterior segment is further divided into inner and outer BRB.…”

Expression, activity and pharmacokinetic impact of ocular transporters

“…The BAB expresses several efflux and influx transporters (Table 3, Figure 5B). In vivo studies on transporter function in the BAB are complicated by the difficulty of separating the impact of the blood-retinal barrier (BRB) and even the corneal barriers in some cases [53]. Still, there are several reports supporting MDR1 activity in the BAB [54][55][56].…”

Use of biomaterials for sustained delivery of anti-VEGF to treat retinal diseases

“…These barriers result in less than 5% of topical medications reaching the anterior segment of the eye [ 25 ]. Once in the anterior segment, drug transporters in the iris–ciliary body also actively eliminate drug from the aqueous humour, reducing its ocular bioavailability [ 26 ]. Figure 1 illustrates the various barriers of delivery associated with topical administration of anti-VEGF compounds.…”