biostudies-literatureKim ENIH HHS4128https://www.ebi.ac.uk/biostudies/studies/S-EPMC10011522biostudies-literatureUnknown13(1)The efficacy of many anti-epileptic drugs, including phenytoin (PHT), is reduced by plasma protein binding (PPB) that sequesters therapeutically active drug molecules within the bloodstream. An increase in systemic dose elevates the risk of drug side effects, which demands an alternative technique to increase the unbound concentration of PHT in a region-specific manner. We present a low-intensity focused ultrasound (FUS) technique that locally enhances the efficacy of PHT by transiently disrupting its binding to albumin. We first identified the acoustic parameters that yielded the highest PHT unbinding from albumin among evaluated parameter sets using equilibrium dialysis. Then, rats with chronic mesial temporal lobe epilepsy (mTLE) received four sessions of PHT injection, each followed byScientific reportsTranscranial focused ultrasound-mediated unbinding of phenytoin from plasma proteins for suppression of chronic temporal lobe epilepsy in a rodent model.PMC10011522R21 EY031807Bohlke MKim EVan Reet JKim HCYoo SSLee WfalseTranscranial focused ultrasound-mediated unbinding of phenytoin from plasma proteins for suppression of chronic temporal lobe epilepsy in a rodent model.The efficacy of many anti-epileptic drugs, including phenytoin (PHT), is reduced by plasma protein binding (PPB) that sequesters therapeutically active drug molecules within the bloodstream. An increase in systemic dose elevates the risk of drug side effects, which demands an alternative technique to increase the unbound concentration of PHT in a region-specific manner. We present a low-intensity focused ultrasound (FUS) technique that locally enhances the efficacy of PHT by transiently disrupting its binding to albumin. We first identified the acoustic parameters that yielded the highest PHT unbinding from albumin among evaluated parameter sets using equilibrium dialysis. Then, rats with chronic mesial temporal lobe epilepsy (mTLE) received four sessions of PHT injection, each followed by2023-01-01T00:00:00Z2023 Mar2025-04-19T02:02:48.04Z2025-04-07T12:41:49.654ZS-EPMC100115223691477510.1038/s41598-023-31383-4