L-Type amino acid transporter 1 as a target for drug delivery

• Verfasst von: Puris, Elena [VerfasserIn]
• Verfasst von: Gynther, Mikko [VerfasserIn]
• Verfasst von: Auriola, Seppo [VerfasserIn]
• Verfasst von: Huttunen, Kristiina M. [VerfasserIn]
• Titel: L-Type amino acid transporter 1 as a target for drug delivery
• Verf.angabe: Elena Puris, Mikko Gynther, Seppo Auriola, Kristiina M. Huttunen
• E-Jahr: 2020
• Jahr: 06 May 2020
• Umfang: 17 S.
• Fussnoten: Gesehen am 28.05.2020
• Titel Quelle: Enthalten in: Pharmaceutical research
• Ort Quelle: Dordrecht [u.a.] : Springer Science + Business Media B.V, 1984
• Jahr Quelle: 2020
• Band/Heft Quelle: 37(2020) Artikel-Nummer 88, 17 Seiten
• ISSN Quelle: 1573-904X
• DOI: doi:10.1007/s11095-020-02826-8
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1698938373

Abstract

Our growing understanding of membrane transporters and their substrate specificity has opened a new avenue in the field of targeted drug delivery. The L-type amino acid transporter 1 (LAT1) has been one of the most extensively investigated transporters for delivering drugs across biological barriers. The transporter is predominantly expressed in cerebral cortex, blood-brain barrier, blood-retina barrier, testis, placenta, bone marrow and several types of cancer. Its physiological function is to mediate Na+ and pH independent exchange of essential amino acids: leucine, phenylalanine, etc. Several drugs and prodrugs designed as LAT1 substrates have been developed to improve targeted delivery into the brain and cancer cells. 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. These examples provide supporting evidence for the utility of the LAT1-mediated targeted delivery of the (pro)drug. This review comprehensively summarizes recent advances in LAT1-mediated targeted drug delivery. In addition, the use of LAT1 is critically evaluated and limitations of the approach are discussed.