Using poly(3,4-ethylenedioxythiophene) polystyrene sulfonate surfaces to develop an electroanalytical sensor for therapeutic monitoring of tricyclic-antidepressants

Gibney, Steven (2022) Using poly(3,4-ethylenedioxythiophene) polystyrene sulfonate surfaces to develop an electroanalytical sensor for therapeutic monitoring of tricyclic-antidepressants. PhD thesis, University of Nottingham.

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This project aims to develop an electroanalytical sensor capable of measuring the real-time concentration of tricyclic antidepressants (TCA) in complex biological environments. Advances in micro- and nano- scale engineering have opened new avenues of sensor development; it is now possible to design sensors which function in vivo. The ability to accurately measure the concentration of an analyte in vivo provides crucial information about the pharmacokinetic behaviour of an analyte, while avoiding the need for repeated and potentially difficult sampling procedures. The main challenges which limit the development of an in vivo sensing device are caused by immune response, inflammation and surface contamination, all of which can prevent a sensor from functioning. To overcome these challenges a multidisciplinary approach must be used. Through a combination of electroanalytical chemistry and biomaterial development I have attempted to design and develop a sensing platform capable of the in vivo detection and monitoring of tricyclic antidepressant (TCA).

Initially, I studied the electrochemical behaviour of the TCA compounds to provide electroanalytical insight that would support the development of an effective sensor. I studied the redox activity of six TCA compounds: imipramine, desipramine, trimipramine, clomipramine, nortriptyline and doxepin. An unmodified glassy carbon electrode was used to perform scan rate studies and generate diagnostics plots for each of the TCA compounds in phosphate buffer solution (versus Ag/AgCl). Comparison of voltammograms, and analysis of peak current vs scan rate, confirmed that the oxidation of the central nitrogen in the TCA structure is irreversible and diffusion-limited. This was further reinforced by plots of current function which supported previous mechanistic data. I also identified variation between clomipramine and other members of the TCA family, in particular a shift in peak current caused by the presence of Cl- in the TCA ring structure.

Next, the conductive polymer Poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) was selected as a potential surface for the development of a sensor; it has shown promise in both sensing and implantable bioelectronic technology. I sought to investigate how the electrical and morphological properties of PEDOT:PSS films changed when mixed or blended with additional components. In this work, I used tunnelling atomic force microscopy (TUNA AFM) paired with Peak Force mode to investigate a PEDOT:PSS polyvinyl alcohol blend. I studied how the properties of a polymer film, made from a blend of PEDOT:PSS and polyvinyl alcohol (PVA), changed with increasing PEDOT:PSS concentration. Surface analysis showed that the level of aggregation in these films increased with increasing concentration of PEDOT:PSS. Further investigation was carried out into how various additives, such as Dimethyl sulfoxide and Divinyl sulfone, changed the morphological and electrical behaviour of PEDOT:PSS films. Peak Force TUNA AFM proved to be an effective method for studying modified PEDOT:PSS films and provided insight about the electrical behaviour of PEDOT which informed the design of a PEDOT based sensor.

Finally, I attempted to design a biodegradable scaffold that could house a PEDOT:PSS formulation and be used to electrochemically detect the redox behaviour of TCA compounds. This work involved the use of 3D extrusion printing to generate a biodegradable scaffold using the commercially available RESOMERĀ® (LR708), a biodegradable polymer. I designed scaffolds and optimised the printing parameters to produce scaffolds which could be used as biodegradable implants. Following this, I characterised the electrochemical behaviour of scaffolds loaded with PEDOT:PSS, using them to detect both an ideal electrochemical analyte and a therapeutically relevant compound, in this case TCA.

This project acts as a proof-of-concept for a biodegradable sensor for the monitoring of electrochemically active therapeutic compounds. Given further development this work could be translated to a clinical setting and contribute towards the growing fields of both bioelectronics and personalised medicine.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Rawson, Frankie
Hook, Andrew
Smith, Paul
Keywords: Tricyclic-antidepressants, TCA
Subjects: R Medicine > RM Therapeutics. Pharmacology
Faculties/Schools: UK Campuses > Faculty of Science > School of Pharmacy
Item ID: 69563
Depositing User: Gibney, Steven
Date Deposited: 31 Dec 2022 04:40
Last Modified: 31 Dec 2022 04:40

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