title: Continuous monitoring of Naproxen by a cytochrome P450-based electrochemical sensor.
abstract: This paper reports the characterization of an electrochemical biosensor for the continuous monitoring of Naproxen based on cytochrome P450. The electrochemical biosensor is based on the drop-casting of multi-walled carbon-nanotubes (MWCNTs) and microsomal cytochrome P4501A2 (msCYP1A2) on a graphite screen-printed electrode (SPE). The proposed biosensor was employed to monitor Naproxen (NAP), a well-known anti-inflammatory compound, through cyclic voltammetry. The dynamic linear range for the amperometric detection of NAP had an upper limit of 300 µM with a corresponding limit of detection (LOD) of 16 ± 1 µM (S/N=3), which is included in NAP physiological range (9-300 µM). The MWCNT/msCYP1A2-SPE sensor was also calibrated for NAP detection in mouse serum that was previously extracted from mice, showing a slightly higher LOD (33 ± 18 µM). The stability of the msCYP1A2-based biosensor was assessed by longtime continuous cyclic voltammetric measurements. The ability of the sensor to monitor drug delivery was investigated by using a commercial micro-osmotic pump. Results show that the MWCNT/msCYP1A2-SPE sensor is capable of precisely monitoring the real-time delivery of NAP for 16 h. This work proves that the proposed electrochemical sensor might represent an innovative point-of-care solution for the personalization of drug therapies, as well as for pharmacokinetic studies in both animals and humans.
authors.affiliation: Laboratory of Integrated Systems, EPFL - École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. Electronic address: camilla.baj-rossi@epfl.ch.
authors.forename: C
authors.initials: C
authors.lastname: Baj-Rossi
authors.forename: T
authors.initials: T
authors.lastname: Rezzonico Jost
authors.forename: A
authors.initials: A
authors.lastname: Cavallini
authors.forename: F
authors.initials: F
authors.lastname: Grassi
authors.forename: G
authors.initials: G
authors.lastname: De Micheli
authors.forename: S
authors.initials: S
authors.lastname: Carrara
mesh_terms: D000818:Animals; D015374:Biosensing Techniques / Q000379:methods*; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry*; D004566:Electrodes; D006801:Humans; D057230:Limit of Detection; D051379:Mice; D037742:Nanotubes, Carbon / Q000737:chemistry; D009288:Naproxen / Q000097:blood / Q000302:isolation & purification*; D010084:Oxidation-Reduction
chemical_list: D037742:Nanotubes, Carbon; D009288:Naproxen; D003577:Cytochrome P-450 Enzyme System
keywords: Carbon nanotubes; Continuous drug monitoring; Cytochrome P450; Electrochemical biosensors; Personalized therapy