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DRUG DELIVERY NANOCARRIERS

PROJECT — Microfluidic based production of non-viral nanosized nucleic acids delivery systems

Poject contact person: Prof. Ida Genta and Dr. Enrica Chiesa

Principal collaborators: Prof. Olivia Merkel and Dr. Simone Carneiro (Department Pharmazie Ludwig-Maximilians-Universität München), Prof. Alberto Auricchio (Telethon Institute of Genetics and Medicine - TIGEM).

Email – ida.genta@unipv.it; enrica.chiesa@unipv.it

Abstract

The COVID-19 pandemic has catapulted nucleic acids (NA) drugs from a relatively niche technology into the mainstream and it brought forth the need for rapid and precise gene editing technologies to combat the virus. Over the years, several nanoparticles have been extensively investigated to carry NA and protect it from the degradation culminating with the approval of Onpattro® for treatment of Amyloidosis and Moderna and Pfizer’s vaccines to prevent COVID-19 infection. NA delivery offers promise for treating genetic problems, cancer, and other therapeutic ailments, going far beyond the area of infectious diseases. This project faces the optimization of the non-viral and targeted nanosized NA delivery systems to boost the potency and efficacy of nanomedicines. In this frame, microfluidics platforms offer a unique opportunity to screen different types of nanocarriers and to develop nanosystems that can enhance the delivery of gene-editing tools. Here, we use a design of experiments approach to optimize nanocarriers properties and the in vitro performance, envisaging the specific administration.

Keywords – Nucleic acid, mRNA, siRNA, lipid nanoparticles, polymeric nanoparticles

PROJECT — Reducing myocardial stiffening and fibrosis in inflammatory and pro-fibrotic cells using targeted nanocarriers

Poject contact person: Prof. Ida Genta and Dr. Enrica Chiesa

Principal collaborators: Dr. Maurizio Pesce and Dr. Gloria Garofalo (Centro Cardiologico Monzino, IRCCS, Unità di Ingegneria Tissutale Cardiovascolare), Dr. Federica Riva (University of Pavia).

Email – ida.genta@unipv.it; enrica.chiesa@unipv.it

Abstract

Heart failure is a pathology in continuous growth worldwide, characterized by inflammation and a progressive fibrosis decreasing the pumping efficiency of the heart. Inflammatory cells (monocyte/macrophages; ICs) and cardiac fibroblasts (CFs), are involved in myocardial fibrosis by coordinated secretion of pro/anti-inflammatory cytokines and differentiation into ‘myofibroblats’, respectively. Therefore, an extensive remodelling of the cardiac extracellular matrix (ECM) occurs, leading to abundant collagen deposition with a consequent increase in stiffness and a reduced contractility and eccentric or concentric hypertrophy. On the other hand, the finding that ICs and CFs respond to tissue mechanics such as the stiffness of the surrounding matrix or its strain, has disclosed new perspectives to treat myocardial fibrosis with nano-tools interfering with intracellular transduction of mechanical forces. The project will target the mechanically activated YAP/TAZ transcriptional pathway in ICs and CFs with selective delivery of theranostic nanoparticles containing a drug known to abrogate the YAP/TAZ transcriptional activity. The nanoparticles will be functionalized with Hyaluronic Acid, whose CD44 receptor is one of the major antigens expressed by inflammatory and pro-fibrotic cells in the failing heart.

Keywords – Heart failure, Cardiac fibrosis, Theranostic Smart Nanoparticles

PROJECT — Microfluidic production station for Nanomedicine

Poject contact person: Dr. Enrica Chiesa, Dr. Alessandro Caimi, Prof. Ida Genta, Prof. Ferdinando Auricchio

Email – ida.genta@unipv.it; enrica.chiesa@unipv.it

Abstract

Starting from a strong and consolidate collaboration with the CompMech Laboratory of the Department of Civil Engineering and Architecture, the research project aims at developing a sensorized, remote-controlled, continuous nanoparticles production station able to reduce the dependence on the operator and to guarantee the quality of ready-to-use nanoparticles. The production station development will exploit a wide range of cutting-edge engineering methodology. This device will overcome the limitation of the current approaches aiming at bridging the gap between the large-scale industrial production and the research activities. The feasibility of the new device will be tested for the production of a wide range of nanoparticles (polymer and lipid based).

Keywords – Microfluidic, Nanoparticles, Nanomedicine, Production.