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Separation Techniques and Affinity Interactions Lab

Macroarea: Pharmaceutical Analysis

ERC Sectors: PE5_18 Medicinal chemistry; PE4_5 Analytical Chemistry; PE5_6 New materials: oxides, alloys, composite, organic-inorganic hybrid, nanoparticles; PE11_9 Nanomaterials engineering, e.g. nanoparticles, nanoporous materials, 1D & 2D nanomaterials; LS7_3 Nanomedicine; LS7_2 Medical technologies and tools (including genetic tools and biomarkers) for prevention, diagnosis, monitoring and treatment of diseases.

Research Team

Lab Managers: Ersilia De Lorenzi (Full Professor), Francesca Gado (Associate Professor), Massimo Serra (Technician)

Junior Staff: Ayesha Khalid (PhD student)

Research Lines

1. CHARACTERIZATION OF MOLECULARLY IMPRINTED NANOPARTICLES. Molecularly Imprinted polymers (MIPs) are designed in-house to detect and sense previously inaccessible tumor markers or to discover novel disease biomarkers. MIPs are characterized during their design and development for final material optimization and reproducibility. Characterization of MIPs in different formats, including nanoparticles is carried out by capillary electrophoresis (CE), liquid chromatography (LC), dynamic light scattering, zeta potential, atomic force microscopy. Template-MIP interaction studies are performed by affinity CE (dynamic complexation CE, frontal CE) and frontal LC. 

2. ANALYSIS AND CHARACTERIZATION OF PROTEINS AS DRUG TARGETS. Advanced analytical and spectroscopic techniques for separation, identification, characterization, quantification and evaluation of proteins as drug targets (charge variants, folding conformers and/or aggregates of proteins with pathological or therapeutic potential). In particular studies are carried out on amyloidogenic proteins.

3. FROM AFFINITY STUDIES TO DRUG DISCOVERY. Integrated strategies to correlate aggregation state, structure and toxicity of Aß 1-42 oligomers as drug targets (capillary electrophoresis, ATR-FTIR, TEM, in silico simulations, biological tests on cell lines). Evaluation of novel curcumin analogues as a potential therapeutic agents against Alzheimer’s Disease. Anti-oligomeric, anti-fibrillogenic, anti-inflammatory, anti-oxidant activity are investigated on cell lines, primary neuronal cells or peripheral blood mononuclear cells from AD patients.

Publications
  • Contardi C. et al: RATIONAL DESIGN OF HIGHLY SELECTIVE SIALYLLACTOSE-IMPRINTED NANOGELS (2024) Chemistry-A European Journal 30(45), e202401232. DOI: 10.1002/chem.202401232
  • Contardi C. et al: AFFINITY CAPILLARY ELECTROPHORESIS AS A TOOL TO CHARACTERIZE MOLECULARLY IMPRINTED NANOGELS IN SOLUTION (2024) Analytical Chemistry, 96, 3017-3024. Awarded with the Front Cover. DOI: 10.1021/acs.analchem.3c04912
  • De Lorenzi E. et al: TARGETING THE MULTIFACETED NEUROTOXICITY OF ALZHEIMER’S DISEASE BY TAILORED FUNCTIONALISATION OF THE CURCUMIN SCAFFOLD (2023) European Journal of Medicinal Chemistry, 252, pp. 115297. DOI: 10.1016/j.ejmech.2023.115297
  • De Lorenzi E. et al: MODULATION OF AMYLOID-INDUCED MICROGLIA ACTIVATION AND NEURONAL CELL DEATH BY CURCUMIN AND ANALOGUES (2022) International Journal of Molecular Sciences, 23, 4381. DOI: 10.3390/ijms23084381
  • Groves, K. et al: REFERENCE PROTOCOL TO ASSESS ANALYTICAL PERFORMANCE OF HIGHER ORDER STRUCTURAL ANALYSIS MEASUREMENTS: RESULTS FROM AN INTERLABORATORY COMPARISON (2021) Analytical Chemistry, 93(26), pp. 9041-9048. DOI: 10.1021/acs.analchem.0c04625
  • Bisceglia, F. et al: PRENYLATED CURCUMIN ANALOGUES AS MULTIPOTENT TOOLS TO TACKLE ALZHEIMER'S DISEASE (2019) ACS Chemical Neuroscience, ACS Chemical Neuroscience, 10(3), pp. 1420-1433. DOI: 10.1021/acschemneuro.8b00463
  • Bisceglia, F. et al: AN INTEGRATED STRATEGY TO CORRELATE AGGREGATION STATE, STRUCTURE AND TOXICITY OF Aß 1–42 OLIGOMERS (2018) Talanta, 188, pp. 17-26. DOI: 10.1016/j.talanta.2018.05.062
  • De Lorenzi, E. et al: EVIDENCE THAT THE HUMAN INNATE IMMUNE PEPTIDE LL-37 MAY BE A BINDING PARTNER OF AMYLOID-Β AND INHIBITOR OF FIBRIL ASSEMBLY (2017) Journal of Alzheimer's Disease, 59(4), pp. 1213-122. DOI: 10.3233/JAD-170223
  • Bertoletti, L. et al: EVALUATION OF CAPILLARY ELECTROPHORESIS-MASS SPECTROMETRY FOR THE ANALYSIS OF THE CONFORMATIONAL HETEROGENEITY OF INTACT PROTEINS USING BETA2-MICROGLOBULIN AS MODEL COMPOUND (2016) Analytica Chimica Acta, 945, pp. 102-109. DOI: 10.1016/j.aca.2016.10.010
  • Brogi, S. et al: DISEASE-MODIFYING ANTI-ALZHEIMER'S DRUGS: INHIBITORS OF HUMAN CHOLINESTERASES INTERFERING WITH Β-AMYLOID AGGREGATION (2014) CNS Neuroscience and Therapeutics, 20(7), pp. 624-632. DOI: 10.1111/cns.12290
Collaborations

National collaborations

ACADEMIC INSTITUTIONS

  • Bice Conti, Rossella Dorati, Cristina Lanni, Department of Drug Sciences, University of Pavia;
  • Maddalena Patrini, Department of Physics, University of Pavia;
  • Morena Zusso, Department of Pharmaceutical and Pharmacological Sciences, University of Padova;
  • Federica Belluti, Department of Pharmacy and Biotechnology, University of Bologna;
  • Giulio Vistoli, Department of Pharmaceutical Sciences, University of Milano Statale;
  • Sofia Giorgetti, Department of Molecular Medicine, University of Pavia;
  • Piersandro Pallavicini, Department of Chemistry, University of Pavia.

INDUSTRY

  • Indena SpA, Settala (MI);
  • Merck-Serono, Guidonia (RM).

International collaborations

ACADEMIC INSTITUTIONS

  • Börje Sellergren, University of Malmö, Sweden;
  • Ian Nicholls, University of Linnaeus, Sweden;
  • Knut Rurack, Federal Institute for Materials Research and Testing, Berlin, Germany;
  • Panagiotis Manesiotis, Queen’s University, Belfast, United Kingdom;
  • Jenny Persson, Umeå University, Sweden.

INDUSTRY

  • Proteome Sciences, Frankfurt, Germany.
Funded active projects

Marie Skłodowska-Curie Actions (HORIZON-MSCA-2024-DN-01 n.101226400- MIPrecise)

Expertise

Competences

Development and validation of analytical methods for small molecules and proteins by capillary electrophoresis (CE-UV), including charge variant profiles of antibodies and pegylated proteins. Feasibility studies and CE method optimization for daily use on drug substance and drug product. Studies on drug-drug, drug-protein, drug-nanoparticle interactions in solution by affinity CE; Analysis of nanoparticles by CE. Development and validation of analytical methods for small molecules and proteins by HPLC-UV, HPLC-DAD. Feasibility studies and HPLC method optimization for daily use on drug substance and drug product.

Instrumentation

n. 3 CE (Agilent and Beckman) with DAD detector; n.2 HPLC (Agilent) with DAD detector; -n. 1 HPLC (Agilent) with UV-Vis detector.

Contacts

ERSILIA DE LORENZI - e-mail: ersidelo@unipv.it - tel. +39 0382 987747