Sviluppo di metodi e sensori elettrochimici per la determinazione di farmaci e markers tumorali in fluidi e tessuti corporei.

In this thesis electroanalytical methods and electrochemical sensor systems were developed to deal with so called Therapeutic Drug Monitoring (TDM) for application in body fluids, or detect specific compounds for early diagnosis of cancer diseases. As for TDM applications, the voltammetric behaviour of the anticancer drug irinotecan (CPT-11), its injectable form in the clinical treatment regimen, irinotecan hydrochloride (CPT-11HCl), and its main metabolites (namely SN-38, SN-38G, APC, and NPC), and the natural chemical analogous camptothecin (CPT) were investigated in acetonitrile, using glassy carbon (GCE) and platinum electrodes. Based on the voltammetric results, a simple electrochemical method for CPT-11 detection in plasma samples was set-up. The overall procedure included an extraction step of the drug from plasma samples, using acetonitrile as the extraction fluid. This step was necessary to avoid interference due to plasma proteins and other compounds normally present in body fluids, such as uric and ascorbic acid. Similar electrochemical investigations and analytical protocols were performed/developed for Imatinib, an antileukemic drug, mainly used for chronic myeloid leukemia treatments. In the case of Imatinib, Ethyl Acetate (EtOAc), mixed with acetic and phosphoric acid was employed as solvent. The analytical protocol for the detection of Imatinib in plasma samples also included an extraction step, as Imatinib, even more than Irinotecan, strongly bounds with plasma proteins. To transfer the methodology to disposables electrode systems, Inkjet Printed Electrodes (IPEs) were investigated. The IPEs were manufactured with relatively cheap materials and printed over flexible PET substrates. the Working Electrode (WE) and the Counter Electrode (CE) were made of multiwalled Carbon Nanotubes (CNTs); the Reference Electrode (RE) and electrical contacts were made with coalesced silver nanoparticles (AgNPs). UV-curable ink EMD 6415 (Sun Chemical) was used for the first time in this kind of applications. It proved promising to guarantee electrical insulation against the rather aggressive media employed in the work for monitoring the drugs. The thesis comprises also the development of other electrode systems and innovative approaches to establish the interaction of the drugs with specifically designed peptides, this in order to improve: selectivity in TDM applications, high throughput for screening the content of the drugs in the samples and high spatial resolution. These approaches made use of the innovative electroanalytical technique Scanning electrochemical Microscopy (SECM), along with the use of micro- and nano-electrodes. Soft microelectrodes were also fabricated for SECM analysis of tissues. Soft probes work in a peculiar contact mode sliding on the target substrate, thus allowing discrimination between useful electrochemical signals, due to the target analytes, from that due topography of the substrates. The usefulness of the proposed soft-probes for dual chemical properties monitoring was assessed for simultaneous pH and NO (a very poison species for humans) detection, using a double Pt-Au probe. Finally, miniaturized sensors based on single or double barrel microelectrodes, coated with specific compounds, i.e., Room Temperature Ionic Liquids (RTILs) and Inherently Chiral Electroactive Organic Films were also tested for the detection of toxic species in either gaseous or liquid phases.