An Electrochemical Strategy for the Simultaneous Detection of Doxorubicin and Simvastatin for Their Potential Use in the Treatment of Cancer.

Iulia Rus,Cecilia Cristea,Cristina Barbălată,Ioan Tomuță,Alina Porfire,Robert Săndulescu,Mihaela Tertiș

doi:10.3390/bios11010015

Iulia Rus, Cecilia Cristea + Show 5 more

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https://doi.org/10.3390/bios11010015

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Abstract

The aim of this study was to develop a disposable, simple, fast, and sensitive sensor for the simultaneous electrochemical detection of doxorubicin (DOX) and simvastatin (SMV), which could be used in preclinical studies for the development of new pharmaceutical formulations for drug delivery. Firstly, the electrochemical behavior of each molecule was analyzed regarding the influence of electrode material, electrolyte solution, and scan rate. After this, the proper electrode material, electrolyte solution, and scan rate for both active substances were chosen, and a linear sweep voltammetry procedure was optimized for simultaneous detection. Two chronoamperometry procedures were tested, one for the detection of DOX in the presence of SMV, and the other one for the detection of DOX and SMV together. Finally, calibration curves for DOX and SMV in the presence of each other were obtained using both electrochemical methods and the results were compared. The use of amperometry allowed for a better limit of detection (DOX: 0.1 μg/mL; SMV: 0.7 μg/mL) than the one obtained in voltammetry (1.5 μg/mL for both drugs). The limits of quantification using amperometry were 0.5 μg/mL for DOX (dynamic range: 0.5–65 μg/mL) and 2 μg/mL for SMV (dynamic range: 2–65 μg/mL), while using voltammetry 1 μg/mL was obtained for DOX (dynamic range: 1–100 μg/mL) and 5 μg/mL for SMV (dynamic range: 5–100 μg/mL). This detection strategy represents a promising tool for the analysis of new pharmaceutical formulations for targeted drug delivery containing both drugs, whose association was proven to bring benefits in the treatment of cancer.

Highlights

DOX, a compound isolated from natural sources, belongs to the anthracycline class and exhibits very potent activity against numerous types of cancer
The antiproliferative effect of statins stems from their mechanism of action, namely the inhibition of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMGCoA) reductase in cholesterol synthesis [5]
This study describes for the first time the development of a simple and fast simultaneous detection of DOX and SMV using electrochemical techniques and screen printed disposable electrochemical cells

Summary

Introduction

DOX, a compound isolated from natural sources, belongs to the anthracycline class and exhibits very potent activity against numerous types of cancer. Aside from its many pharmacological benefits in cancer therapy, DOX presents severe acute and long-term side effects, including multiple organ toxicity, developed in a dose-dependent manner [1,2]. The antiproliferative effect of statins stems from their mechanism of action, namely the inhibition of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMGCoA) reductase in cholesterol synthesis [5]. Through this pathway, cholesterol synthesis is prevented, and the synthesis of other intermediates, responsible for various processes in the development and metastasis of cancer [5,6]. SMV is the most studied, with numerous in vivo and in vitro studies proving a synergistic or additive effect of SMV in combination with a large number of chemotherapeutic drugs, including

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