DIACHEMO

Point-of-care microfluidic device for quantification of chemotherapeutic drugs in small body fluid samples by highly selective nanoparticle extraction and liquid crystal detection

The goal of this project is to develop a robust and reliable point-of-care sensing device to measure, in real-time and with high precision, the concentration of chemotherapeutic drugs in small samples of body fluids. The objective is to aid the decision making of clinicians on doses and dosage of such drugs in patients by providing a rapid, quantitative, and portable detection system. At present, dosage for chemotherapeutics is based almost exclusively on body surface, and doesn’t take into account the individual variability of metabolic activity and of bio-distribution. The device we propose to develop will provide a reliable and inexpensive way to adapt dosing of anticancer drugs according to patients’ individual drug pharmacokinetics. This is especially required for therapeutic drug monitoring (TDM) of antineoplastic drugs characterized by a low therapeutic index (i.e. narrow toxic-therapeutic range and effective dosage) or in very young patients.

We propose to build a microfluidics-based device, basing on two novel ideas recently developed in the laboratories of Besta and EPFL. First, innovative drug capturing nanoparticles (NPs) will be added to serum extracted from patients’ blood and deprived of the clotting factors, where they selectively bind to drug molecules. Only NPs that have bound to a specific metabolic form of the drug will then transfer into a liquid crystal (LC) phase, where we measure their concentration optically. The concentration of drug in the blood will be directly related to the concentration of the particles in the LC phase. The whole process from serum extraction to optical readout will be integrated in a single completely automated lab-on-a-chip microfluidic system. This device will be validated against current detection method on real patient samples. It will require only small sample volumes and should provide the clinician with a concentration of the drug and of its metabolites in a total time of two hours.

Upcoming Events

NANOSAFE 2020

7th International Conference NANOSAFE

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EUROTOX 2020

Combined efforts in quest of safer chemicals and medicines

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NANO 2020

International Conference on Nanostructured Materials

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Latest News

Consortium Meeting in Sacile

The DIACHEMO Consortium Meeting was organised from 19 – 20 April 2018 in Saclie, Italy. Project partner CRO Aviano organized the meeting. During the two days of the meeting the consortium intensively discussed the design and further development of the prototypes and nanoparticles.

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VERMES joined the Consortium

Starting from 1st February 2018 VERMES joined the consortium as a new partner. VERMES is replacing provenion while the complete provenion staff will join the new medical devices group at VERMES. This means that the knowledge on the device will remain in the project and ensure a smooth continuation of work.

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DIACHEMO Consortium Meeting in Poligano di Mare

The 5th Consortium Meeting of DIACHEMO was organized from 18th to 19th October 2017 in Polignano di Mare (close to Bari, Italy). This meeting has been organized by the coordinator ITGP. After a change in the consortium DIACHEMO partners met again with the External Advisory Board to get their feedback on the work done so far and to discuss in- and externally about the project achievements so far.

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Publications

pH-Mediated molecular differentiation for fluorimetric quantification of chemotherapeutic drugs in human plasma

Luis A. Serrano, Ye Yang, Elisa Salvati, Francesco Stellacci, Silke Krol and Stefan Guldin

At present, drug dosage is based on standardised approaches that disregard pharmakokinetic differences between patients and lead to non-optimal efficacy and unnecessary side effects. In this work, we demonstrate the potential of pH-mediated fluorescence spectroscopy for therapeutic drug monitoring in complex media. We apply this principle to the simultaneous quantification of the chemotherapeutic prodrug Irinotecan and its active metabolite SN-38 from human plasma across the clinically relevant concentration range, i.e. from micromolar to nanomolar at molar ratios of up to 30 : 1.

A new high-performance liquid chromatography-tandem mass spectrometry method for the determination of paclitaxel and 6α-hydroxy-paclitaxel in human plasma: Development, validation and application in a clinical pharmacokinetic study

Bianca Posocco, Mauro Buzzo, Andrea Follegot, Luciana Giodini, Roberto Sorio, Elena Marangon, Giuseppe Toffoli

Paclitaxel belongs to the taxanes family and it is used, alone or in multidrug regimens, for the therapy of several solid tumours, such as breast-, lung-, head and neck-, and ovarian cancer. Standard dosing of chemotherapy does not take into account the many inter-patient differences that make drug exposure highly variable, thus leading to the insurgence of severe toxicity. This is particularly true for paclitaxel considering that a relationship between haematological toxicity and plasma exposure was found. Therefore, in order to treat patients with the correct dose of paclitaxel, improving the overall benefit–risk ratio, Therapeutic Drug Monitoring is necessary. In order to quantify paclitaxel and its main metabolite, 6α-hydroxy-paclitaxel, in patients’ plasma, we developed a new, sensitive and specific HPLC–MS/MS method applicable to all paclitaxel dosages used in clinical routine. The developed method used a small volume of plasma sample and is based on quick protein precipitation. The chromatographic separation of the analytes was achieved with a SunFire™ C18 column (3.5 μM, 92 Å, 2,1 x 150 mm); the mobile phases were 0.1% formic acid/bidistilled water and 0.1% formic acid/acetonitrile. The electrospray ionization source worked in positive ion mode and the mass spectrometer operated in selected reaction monitoring mode. Our bioanalytical method was successfully validated according to the FDA-EMA guidelines on bioanalytical method validation. The calibration curves resulted linear (R2 ≥0.9948) over the concentration ranges (1–10000 ng/mL for paclitaxel and 1–1000 ng/mL for 6α-hydroxy-paclitaxel) and were characterized by a good accuracy and precision. The intra- and inter-day precision and accuracy were determined on three quality control concentrations for paclitaxel and 6α-hydroxy-paclitaxel and resulted respectively <9.9% and within 91.1–114.8%. In addition, to further verify the assay reproducibility, we tested this method by re-analysing the incurred samples. This bioanalytical method was employed with success to a genotype-guided phase Ib study of weekly paclitaxel in ovarian cancer patients treated with a wide range of drug’s dosages.