Revised: June 20, 2012
Accepted: December 1, 2012
Published online: March 9, 2013
The eye is a highly protected organ, and designing an effective therapy is often considered a challenging task. The anatomical and physiological barriers result in low ocular bioavailability of drugs. Due to these constraints, less than 5% of the administered dose is absorbed from the conventional ophthalmic dosage forms. Further, physicochemical properties such as lipophilicity, molecular weight and charge modulate the permeability of drug molecules. Vision-threatening diseases such as glaucoma, diabetic macular edema, cataract, wet and dry age-related macular degeneration, proliferative vitreoretinopathy, uveitis, and cytomegalovirus retinitis alter the pathophysiological and molecular mechanisms. Understanding these mechanisms may result in the development of novel treatment modalities. Recently, transporter/receptor targeted prodrug approach has generated significant interest in ocular drug delivery. These transporters and receptors are involved in the transport of essential nutrients, vitamins, and xenobiotics across biological membranes. Several influx transporters (peptides, amino acids, glucose, lactate and nucleosides/nucleobases) and receptors (folate and biotin) have been identified on conjunctiva, cornea, and retina. Structural and functional delineation of these transporters will enable more drugs targeting the posterior segment to be successfully delivered topically. Prodrug derivatization targeting transporters and receptors expressed on ocular tissues has been the subject of intense research. Several prodrugs have been designed to target these transporters and enhance the absorption of poorly permeating parent drug. Moreover, this approach might be used in gene delivery to modify cellular function and membrane receptors. This review provides comprehensive information on ocular drug delivery, with special emphasis on the use of transporters and receptors to improve drug bioavailability.