Evaluation of brain targeted transporter-utilizing prodrugs of neuroprotective agents

Neurodegenerative diseases are linked to oxidative stress, making antioxidant (AOX) compounds a viable option for both symptom relief and targeting the disease's root cause. Prodrug, one of the modern drug developments emphasizes enhancing drug delivery. The blood-brain barrier (BBB), as an obstacle for the target organ in neurodegenerative conditions. LAT-1 influx enables the enter of amino acids inside the cells and is expressed in BBB remarkably. LAT1-utilizing prodrugs have shown promise due to LAT1's selective expression in the BBB and its overexpression in some cancers. Designing prodrugs with a phenolic AOX promoiety and LAT1 substrate can enhance targeted delivery. The aim of this study was to investigate the cleavage and release time of antioxidant parent drugs from their LAT1-utilizing prodrugs by bioconversion studies in-vitro. These results showed that most of the studied prodrugs are not able to cleave according to HPLC analysis.