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Biocompatible Palladium Telluride Quantum Dot-Amplified Biosensor for HIV Drug

  • Usisipho FeleniEmail author
  • Unathi Sidwaba
  • Nomaphelo Ntshongontshi
  • Lindsay Wilson
  • Emmanuel Iwuoha
Original Research
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Abstract

Indinavir (IDV) is a potent and well-tolerated protease inhibitor antiretroviral (ARV) drug used as a component of the highly active antiretroviral therapy (HAART) of human immunodeficiency virus (HIV). It undergoes hepatic first-pass metabolism that is catalysed by microsomal cytochrome P450-3A4 enzyme (CYP3A4), which results in pharmacokinetics that may be favourable or adverse. Therapeutic drug monitoring (TDM) of IDV during HIV treatment is therefore critical, in order to prevent the adverse effects of its first-pass metabolism and optimise an individual’s dosage regime. Biosensors are now the preferred diagnostic tools for TDM assessment at point-of-care, due to their high sensitivity and real-time response. An electrochemical biosensor for IDV was prepared by depositing a thin film of CYP3A4 (a thiolate enzyme) and thioglycolic acid-capped palladium telluride quantum dot (TGA-PdTeQD) on a cysteamine-functionalised gold disk electrode (Cyst|Au) using a combination of thiol and carbodiimide covalent bonding chemistries. The electrochemical signatures of the biosensor (CYP3A4|TGA-PdTeQD|Cyst|Au) were determined by cyclic voltammetry (CV) that was performed at a scan rate of 500 mV s−1, and the sensor responses at the characteristic reduction peak potential value of − 0.26 V were recorded. The sensitivity, linear range (LR) and limit of detection (LOD) values of the indinavir biosensor were 4.45 ± 0.11 μA nM−1 IDV, 0.5–1.0 nM IDV (i.e. 3.6 × 10−4–7.1 × 10−4 mg L−1 IDV) and 4.5 × 10−4 mg L−1 IDV, respectively. The values of the two analytical parameters (LR and LOD) of the biosensor were by up to four orders of magnitude lower than the maximum plasma concentration (Cmax) values of indinavir (0.13–8.6 mg L−1 IDV). The IDV biosensor was successfully used to detect IDV in human serum samples containing dissolved indinavir tablet. This, therefore, indicates the indinavir biosensor’s suitability for TDM applications, using samples obtained within 1–2 h of drug intake at point-of-care, for which very low levels of the drug are expected.

Graphical abstract

Keywords

Cyclic voltammetry Cytochrome P450-3A4 Electrochemical sensors Human serum Indinavir Limit of detection Palladium telluride quantum dot 

Notes

Funding Information

This work was funded by the South African Department of Science and Technology’s (DST’s) National Nanoscience Postgraduate Teaching and Training Platform (NNPTTP), and the National Research Foundation (NRF) of South Africa Research Chair Initiative Grant Number 85102, for NanoElectrochemistry and Sensor Technology.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Usisipho Feleni
    • 1
    • 2
    Email author
  • Unathi Sidwaba
    • 1
    • 2
  • Nomaphelo Ntshongontshi
    • 1
  • Lindsay Wilson
    • 1
  • Emmanuel Iwuoha
    • 1
  1. 1.SensorLab, Department of ChemistryUniversity of the Western CapeCape TownSouth Africa
  2. 2.Nanotechnology and Water Sustainability Research Unit, College of Science, Engineering and TechnologyUniversity of South Africa, Florida CampusJohannesburgSouth Africa

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