Membrane Permeability Monitoring to Antipsychotic Olanzapine Using Platinum Black-Modified Electrodes

TL;DR

This study uses modified electrodes to monitor the permeability of the antipsychotic drug Olanzapine through a model of the blood-brain barrier.

Contribution

A platinum black-modified electrode is introduced for improved electrochemical monitoring of Olanzapine permeability.

Findings

The modified electrode showed increased current with higher Olanzapine concentrations in phosphate buffer saline.

The detection limit for Olanzapine was calculated as 9.96 ± 7.35 × 10−6 nM.

Membrane permeability was tested using TEER measurements and permeability rate constants from five schizophrenia patients.

Abstract

The blood–brain barrier (BBB) is key to the regular functioning of the central nervous system. The dysfunction of the BBB has been described in various neurological disorders, including schizophrenia. Schizophrenia (SCZ) is a chronic psychiatric disorder described by hallucinations, delusions, and negative symptoms. The Olanzapine (OLZ) drug is an electroactive species, and its levels can be monitored using electrochemical sensors. The detection of OLZ was demonstrated previously by using electrochemical sensors, and this technique can be used to monitor the levels of OLZ in real time. The challenge is to identify the permeability of OLZ through the BBB, so a replica model was designed with the BBB based on a Transwell membrane seeded with endothelial cells. A microfabricated electrode consisting of a 3 mm Au disk was modified with platinum black; this enables higher selectivity of electrochemical signals from OLZ. The dose–response of OLZ was characterized in phosphate buffer saline solution (10 mM, pH 7.4) by adding 20–200 nM (in steps 20) of OLZ stock solution. The observed chronoamperometric electrochemical signals showed an increasing current at 0.45 V vs. Ag/AgCl with an increasing OLZ concentration. The controls for the experiments were performed in phosphate-buffered saline solution (10 mM, pH 7.4). The detection limit was calculated as 9.96 ± 7.35 × 10−6 nM from the calibration curve. The membrane permeability of the OLZ drug tested with five SCZ patients was monitored by studying the TEER measurements and permeability rate constant data.

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