AI Article Synopsis
- Plasma protein binding (PPB) significantly influences the effectiveness of drugs targeting the central nervous system by impacting the amount of drug that can cross the blood-brain barrier (BBB).
- Researchers used a technique called focused ultrasound (FUS) to non-invasively disrupt PPB of phenytoin, an anti-epileptic drug, resulting in a 27.7% increase in the unbound drug concentration.
- In animal studies, targeted FUS treatment of one side of the brain led to enhanced drug uptake in that side without overheating or damaging the BBB, paving the way for potential new approaches in drug delivery.
Article Abstract
Plasma protein binding (PPB) plays an important role in drug pharmacokinetics, particularly for central nervous system drugs, as PPB affects the blood concentration of unbound drug available to cross the blood-brain barrier (BBB). We report the non-invasive, spatially specific disruption of PPB to phenytoin, an anti-epileptic drug with high affinity to albumin, using 250-kHz focused ultrasound (FUS) delivered in a pulsed manner (55-ms tone burst duration, 4-Hz pulse repetitions). Equilibrium dialysis performed on sonicated phosphate-buffered saline solution containing phenytoin and bovine serum albumin revealed a 27.7% elevation in the unbound phenytoin concentration compared with an unsonicated control. Sonication of a unilateral brain hemisphere in rats (n = 10) after intraperitoneal phenytoin injection revealed increased parenchymal phenytoin uptake compared with the unsonicated hemisphere, without evidence of temperature change or BBB disruption. These findings illustrate the use of FUS as a novel technique for spatially selective disruption of PPB, which may be applied to a wide range of drug-plasma protein interactions.
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| http://dx.doi.org/10.1016/j.ultrasmedbio.2020.04.011 | DOI Listing |
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