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The membrane impermeability of a drug poses a significant challenge in drug research and development, preventing effective drug delivery to the target site. Specifically, the blood-brain barrier (BBB) presents a formidable obstacle to the delivery of drugs targeting the central nervous system (CNS) into the brain, whereas the blood-retinal barrier (BRB) presents a tremendous obstacle to the delivery of drugs targeting the ocular diseases into the eyes. The development of drugs for Alzheimer's or Parkinson's disease targeting the CNS and for diabetic retinopathy and age-related macular degeneration targeting the eyes remains an unmet medical need for patients. Transporters play a crucial physiological role in maintaining homeostasis in metabolic organs. Various types of solute carrier (SLC) transporters are expressed in the capillary endothelial cells of the BBB, facilitating the delivery of nutrients from the blood flow to the brain. Therefore, carrier-mediated transport across the BBB can be achieved using SLC transporters present in capillary endothelial cells. It is well-known that CNS drugs typically incorporate N-containing groups, indicating that cation transporters facilitate their transport into the brain. In fact, carrier-mediated transport across the BBB can be accomplished using glucose transporter type 1 (Glut1) as a glucose transporter, L-type amino acid transporter 1 (LAT1) as a large neutral amino acid transporter, and H+/cation antiporter as a cation transporter. Surprisingly, although organic cation transporter novel type 2 (OCTN2) is expressed in the capillary endothelial cells, there has been limited investigation into OCTN2-mediated substance delivery into the brain across the BBB. Furthermore, it is suggested that OCTN2 is expressed at the BRB. In this prospective review, I present the advantages and possibilities of substance delivery into the brain across the BBB or into the eyes across the BRB, mediated by OCTN2 via carrier-mediated transport or receptor-mediated transcytosis. [ABSTRACT FROM AUTHOR]

The impact of visual impairment, such as blindness, on quality of life is immeasurable. However, effective ocular drug delivery into the eyes has not yet been established, primarily due to the impermeability imposed by the blood–retinal barrier (BRB) based on the tight junctions and efflux transporters at the endothelium or the epithelium in oral or intravenous administration, as well as the dilution with tear fluid and excretion through the nasolacrimal duct in eye drop administration. Furthermore, intravitreous injections induce pain and fear in patients. Unmet medical needs persist in ocular diseases such as age-related macular degeneration and diabetic retinopathy. Therefore, innovative non-invasive administration methods should be developed. Drug-releasing soft contact lenses (DR-SCLs) affixed to the eye's surface can continuously and locally deliver their loaded drugs to the eyes. The use of DR-SCLs is expected to greatly enhance the bioavailability and patient adherence to the drug regimen. It is known that several solute carrier (SLC) transporters are expressed in various parts of the eyes, including the cornea, the ciliary body, and the bulbar conjunctiva. Carrier-mediated transport through SLC transporters may occur in addition to passive diffusion. Moreover, nanoparticles can be loaded into DR-SCLs, offering various intelligent approaches based on modifications to induce receptor-mediated endocytosis/transcytosis or to control the loaded drug release within this delivery system. In this perspective review, I discuss the implementation and potential of DR-SCL-mediated ocular drug delivery, particularly focusing on low-molecular-weight compounds because of their fine distribution in living body, ease of handling, and ease of manufacturing. [ABSTRACT FROM AUTHOR]