![]() In addition, the limitations and advantages of the approach are discussed. ![]() In the present review, the current state of the art and recent improvements in the LAT1-mediated drug delivery are summarized. This suggests that effective drug delivery to the target organ expressing LAT1 can be achieved by rational design of the drugs mimicking the structures of the transporter endogenous substrates. Importantly, the transporter has already demonstrated its utility by mediating the brain delivery of the antiparkinsonian drug L-Dopa and the anticancer drug, melphalan ( 5, 6). In this respect, the L-type amino acid transporter 1 (LAT1, SLC7A5), which is expressed at a relatively high level at the blood-brain barrier (BBB), blood-retinal barrier (BRB), testis, bone marrow, placenta and several types of human tumour is an intriguing way for targeting a drug to these organs. The design of drugs or prodrugs as substrates of the particular membrane transporter can enable targeted delivery of the drug based on the tissue specific expression profile of the carrier. One of the most promising approaches is the utilization of the transporters selectively expressed at the cell membrane of the target tissue ( 3, 4). In addition to direct administration of the drug by some specific route to the target organ, several other strategies have been investigated including nanoparticle-based drug delivery systems, prodrugs or derivatives and stimuli sensitive targeted therapy ( 1, 2). Delivery of the drug to the site where the target is located requires knowledge about the tissue and an understanding of what features the drug should possess in order to be selectively distributed. ![]() The main aim of targeted drug delivery is to achieve therapeutic concentrations of the drug at the site of action in the tissue of interest to produce the desired pharmacological effect as well as minimizing the side effects caused by drug distribution to other organs. In addition, the use of LAT1 is critically evaluated and limitations of the approach are discussed. This review comprehensively summarizes recent advances in LAT1-mediated targeted drug delivery. These examples provide supporting evidence for the utility of the LAT1-mediated targeted delivery of the (pro)drug. ![]() Thus, the anti-parkinsonian drug, L-Dopa, the anti-cancer drug, melphalan and the anti-epileptic drug gabapentin, all used in clinical practice, utilize LAT1 to reach their target site. Several drugs and prodrugs designed as LAT1 substrates have been developed to improve targeted delivery into the brain and cancer cells. Its physiological function is to mediate Na + and pH independent exchange of essential amino acids: leucine, phenylalanine, etc. ![]() The transporter is predominantly expressed in cerebral cortex, blood-brain barrier, blood-retina barrier, testis, placenta, bone marrow and several types of cancer. The L-type amino acid transporter 1 (LAT1) has been one of the most extensively investigated transporters for delivering drugs across biological barriers. Our growing understanding of membrane transporters and their substrate specificity has opened a new avenue in the field of targeted drug delivery. ![]()
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