Pharmaceutical Technology & Law (PT&L)

Macroarea: Pharmaceutical technology

ERC Sectors: LS7_3 Nanomedicine; LS7_4 Regenerative medicine; LS7_12 Health care, including care for the ageing population

Lab Managers: Bice Conti (PO), Ida Genta (PA), Tiziana Modena (PO), Rosella Dorati (PA), Enrica Chiesa (RTDA), Silvia Pisani (RTD/A)

Junior Staff:  Antonietta Greco (Dottoranda), Mariella Rosalia (Dottoranda), Erika Maria Tottoli (Dottoranda)

1. Nanomedicine

Nanomedicine refers to the therapeutic application of nanoparticulate carriers, exploiting their unique characteristics to optimize the treatment of various diseases while minimizing side effects. The research line involves the design and formulation of biodegradable nanoparticulate systems of polymeric (nanospheres, nanocapsules) and lipidic nature (liposomes, lipid nanoparticles), suitable for the controlled release of drugs, synthetic compounds (small molecules), and/or macromolecules. Specifically, biodegradable polymers of natural origin (e.g., chitosan, hyaluronic acid, and their derivatives) and synthetic (polylactides, polylactide-co-glycolides, polycaprolactones, and PEGylated derivatives) are employed. The research includes the development of lipidic and polymeric "smart" nanocarriers, i.e., suitable for the selective release of active agents to biological targets to achieve a more specific therapeutic or theranostic effect. Nanocarriers are produced using innovative microfluidic techniques as well as traditional ones. The research is interdisciplinary, involving technological-formulative, biological-pharmacological, medical, and regulatory skills.

Current projects include:
- Design and formulation of "smart" polymeric nanoparticles selective for the treatment of desmoplastic tumors (e.g., triple-negative breast cancer, pancreas).
- Design and formulation of liposomes and lipid nanoparticles for the selective delivery of nucleic acids.
- Design and formulation of biodegradable polymeric nanoparticles with theranostic properties (delivery of drugs and diagnostic agents).
- Design and formulation of "smart" polymeric nanoparticles selective for the treatment of cardiac fibrosis.
- Study of a more versatile microfluidic device for the production of polymeric and lipidic nanocarriers.

2. Tissue Engineering

This research line focuses on investigating biodegradable polymeric scaffolds for tissue regeneration, primarily exploiting the properties of nanofibrous scaffolds obtained with advanced and innovative production technologies such as electrospinning and 3D(bio)printing. Polymeric scaffolds are designed and developed by modulating their characteristics based on the organ/tissue to be regenerated. The design of scaffolds as therapeutic systems for the delivery of anti-inflammatory and antibacterial drugs is also studied to reduce inflammatory response and prevent possible infections following implantation in the human body. The research is interdisciplinary, involving technological-formulative, biological-pharmacological, medical, and regulatory skills. Specifically, current projects are aimed at:
- Esophagus: Design of biomimetic scaffolds for esophageal replacement.
- Shape memory: Application of shape memory properties of polymers in the development of engineered scaffolds.
- Vascular scaffolds: Design of small vessel substitutes obtained by electrospinning synthetic biodegradable polymers combined with non-natural peptide or peptidomimetic molecules.
- Electrospinning of non-polymeric materials, peptides, and peptidomimetics for biomedical use.
- Electrospinning of tubular scaffolds carrying anti-inflammatory and antibacterial drugs already in use in therapy (repurposing old drugs).

3. Wound Healing

The research line is largely focused on designing and developing new advanced dressings for the treatment of complex wounds. The research will focus on experimenting with different therapeutic approaches (natural and synthetic compounds, and siRNA) aimed at wound healing and modulation of hypertrophic scarring. Biomaterials offer an interesting option for wound care as they can provide a protective environment for the wound and perform versatile functions. The entire project addresses various aspects such as pharmaceutical technology, biological, microbiological, and animal studies in vitro and in vivo; all these aspects are developed considering regulatory aspects.

4. Medical Devices (Circular Economy)

The research line aims to enhance a secondary raw material obtained from plant waste for its use in the biomedical field. This secondary raw material is biodegradable and has antibacterial activity, making it very interesting for its application in the development of completely biodegradable medical devices. The project is in collaboration with the University of Milan and the Polytechnic University of Milan. Our group is involved in various aspects such as the design and development of medical devices, biological, microbiological, and animal studies in vitro and in vivo; all these aspects are developed considering regulatory aspects.

• Pisani S., Calcaterra V., Croce S., Dorati R., Bruni G., Genta I., Avanzini A., Benazzo M., Pelizzo G., Conti B., Shape memory engineered scaffold (SMES) for potential repair of neural tube defects, Reactive and Functional Polymers, 173, 2022, 105223. https://doi.org/10.1016/j.reactfunctpolym.2022.105223.
• Pisani S., Croce S., Mauramati S., Marmonti M., Cobianchi L., Herman I., Dorati R., Avanzini M.A, Genta I., Benazzo M., Conti B. Engineered Full Thickness Electrospun Scaffold for Esophageal Tissue Regeneration: From In Vitro to In Vivo Approach Pharmaceutics 14, 2022 2:252. https://doi.org/10.3390/pharmaceutics14020252
• Mariotti C.E., Ramos-Rivera L., Conti B., Boccaccini A.R. Zein-Based Electrospun Fibers Containing Bioactive Glass with Antibacterial Capabilities. Macromol Biosci. 2020 20(7):e2000059. https://doi: 10.1002/mabi.202000059
• Chiesa E., Greco A., Dorati R., Conti B., Bruni G., D. Lamprou, Genta I., Microfluidic-assisted synthesis of multifunctional iodinated contrast agent polymeric nanoplatforms. Int. J. Pharm. 2021, 599, 120447. https://doi: 10.1016/j.ijpharm.2021.120447
• Chiesa E., Riva F., Dorati R., Greco A., Ricci S., Pisani S., Patrini M., Modena T., Conti B., Genta I. On-Chip Synthesis of Hyaluronic Acid-Based Nanoparticles for Selective Inhibition of CD44+ Human Mesenchymal Stem Cell Proliferation.  Pharmaceutics 2020; 12(3), 260. https://doi:10.3390/pharmaceutics12030260
• Chiesa E., Greco A., Riva F., Tosca E.M., Dorati R., Pisani S., Modena T., Conti B., Genta I.,   Staggered herringbone microfluid device for the manufacturing of chitosan/TPP nanoparticles: Systematic optimization and preliminary biological evaluation. Int. J. Mol. Sci. 2019; 20(24), 6212. https://doi:10.3390/ijms2024621
• Tottoli E. M., Dorati, R. Genta, I. Chiesa, E. Pisani, S., Conti, B. Skin Wound Healing Process and New Emerging Technologies for Skin Wound Care and Regeneration. Pharmaceutics, 2020; 12(8), 735. https://doi.org/10.3390/pharmaceutics120807358.
• Dorati R., Medina J.L., DeLuca P.P., Leung K.P. Development of a Topical 48-H Release Formulation as an Anti-scarring Treatment for Deep Partial-Thickness Burns. AAPS PharmSciTech. 2018; 19(5):2264-2275. https://doi.10.1208/s12249-018-1030-3.
• Medina J.L., Sebastian E.A., Fourcaudot A.B., Dorati R., Leung K.P. Pirfenidone Ointment Modulates the Burn Wound Bed in C57BL/6 Mice by Suppressing Inflammatory Responses. Inflammation. 2019; 42(1):45-53. https://doi.org/10.1007/s10753-018-0871-y.
• Rosalia M., Ravipati P., Grisoli P., Dorati R., Genta I., Chiesa E., Bruni G., Conti B. Tobramycin Supplemented Small-Diameter Vascular Grafts for Local Antibiotic Delivery: A Preliminary Formulation Study International Journal of Molecular Sciences 22, 2021; 24:13557. https://doi.org/10.3390/ijms222413557

National Collaborations

• Istituti Italiano di Tecnologia – IIT (Dr. Paolo Decuzzi, Prof. N. Tirelli)
• Università di Padova (Proff. P. Caliceti and S. Salmaso)
• Università di Milano (Proff. P. Minghetti, S.P.M. Trasatti, M.L. Gelmi, F. Clerici, S. Pellegrino, R. Bucci)
• Politecnico di Milano (Prof. S. E. R. Turri, Dr. Raffaella Suriano),
• Policlinico San Matteo Fondazione IRCCS (Proff. Marco Benazzo, Teresa Rampino, Dr. Maria Antonietta Avanzini)
• ICS S. Maugeri (Dr. Marco Mario Tre Soldi)
• Università di Bologna (Dr. Domenico Ventrella)
• Università degli studi di Insubria (Proff. Rosalba Gornati, Federica Rossi)
• Istituto Cardiologico Monzino (Dr. M. Pesce)

International Collaborations

• Queen’s University Belfast (Prof. Dimitrios Lamprou)
• University of Minho (Profs. Rui Reis and Vitor Corelo)
• University of Erlangen-Nuremberg (Prof. A. Boccaccini)
• U.S. Army Institute of Surgical Research, US Army Institute of Surgical Research (Dr. Kai P Leung)
• Trinity College Dublin (Prof. Adriele Prina-Mello)
• Ben-Gurion University of the Negev | BGU (Prof. Stepensky David)
• Ludwig-Maximilians-Universität München (Prof. Olivia Merkel),
• University of Patras (Sophia Antimisisaris)
• University of Crete (Stratakis, Emmanuel)
• Ghent University (Prof. K. Braeckmans)
• Universitat Politecnica de Catalunya (Prof. C. Aleman)
• The Hebrew University of Jerusalem (Prof. M. Reches)
• Universite de Montpellier (Prof. G. Subra)
• Asociacion Centro de Investigacion Cooperativa en Nanociencias CIC Nanogune (Prof. A. Bittner).

• NANOREMEDI - 101072645 - GAP-101072645 H2020 HORIZON-MSCA-2021-DN-01, proposal # 101072645 Proposal Title: Functional Nanoscaffolds for Regenerative Medicine.
• Fondazione Cariplo per Economia Circolare 2021, PI of UniPV Research Unit: Cutin from tomato-peel waste: green source for plurality of engineered polymer products (CutToPro), starting in April 2022-ongoing.
• Fondazione Cariplo 2020 Integrated platform for the sustainable production of bio-based surfactants from renewable resources (BioSurf), Rif. 2020-1094 – Bando 2020 – Economia Circolare: ricerca per un futuro sostenibile. 2020-ongoing,
• Grant Regione Lombardia, Bio/nanotech @UniPV per Energia Sostenibile e Salute, 2020- ongoing. # CE4WE.
• Call “Hub Ricerca e Innovazione” cofounded by POR FESR 2014-2020 Innovazione e Competitività Fluidica Digitale per le Scienze della Vita - DSF (Digital Smart Fluidics), CUP E11B19000810007.
• Ricerca Corrente 2021 Grant IRCCS Policlinico S. Matteo - Effects of hypothermic oxygenated perfusion with Hepatocyte Growth Factor loaded Extracellular Vesicles on ischemic /reperfusion damage in a pig model of kidney transplantation from donor after circulatory death: a new strategy of drug delivery to condition kidney before transplantation, grant # 08054221 (Project life: 36 Months, 2020-ongoing) PI: Teresa Rampino.
• Ricerca Corrente 2021 Grant, IRCCS Policlinico S. Matteo - 3D-hybrid engineered tubular bioscaffold for esophageal tissue regeneration: from in vitro to in vivo validation, project # 08053921, Ricerca Corrente 2021 Grant, IRCCS Policlinico S. Matteo Pavia (Project life: 36 Months, 2021-ongoing) PI: Marco Benazzo.
• VV3TT POC Venture Program Edition 2020, BIOFIBER Advanced Textured Fiber Dressing.

• controlled release systems
• Characterization of polymers
• Characterization of nanoparticulate systems (size and zeta potential)
• Cytotoxicity evaluation according to BS EN 13726 standard
• Biological evaluation of medical devices according to ISO 10993-5 standard
• Stability testing according to ICHQ1a
• Health communication and clinical pharmacy: information to prevent medication errors by patients.
• Microfluidic platforms (Nanoassemblr (Precision Nanosystems) and home-made devices with different geometries), Dynamic Light Scattering (DLS), GMP-oriented Electrospinning, 3D (bio)printer, Microencapsulator (Buchi), Gel permeation Chromatography (columns for hydrophobic and hydrophilic compounds), HPLC (UV detector), ESM Motorized Force Tester equipped with Force Gauge M5 (Mark-10), constant climatic chamber HPP 260 (Memmert), Rheometer (Kinexius Pro+ Malvern), Dynamic Light Scattering (DLS), lyophilizer Lio 5P (Cinquepascal srl, Italy), UV-vis spectrophotometers (JenWay, mod.6750 - Beckman/Coulter mod.DU 7500), equipped cell culture facility.