Mariana Varna

University of Paris-Saclay, France

Title: New Nanoparticle Formulation for Cyclosporin A: In Vitro Assessment

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Biography

Mariana VARNA received her Ph.D. in Biology and Biotechnology at Paris Diderot University (Paris, France). After completing a first postdoctoral fellowship on stem cells and tumor resistance she joined Institut Langevin at ESPCI (Superior School of Physics and Industrial Chemistry, Paris, France) for a second post-doctorate on nanomedicines. Since 2015, she is Associate Professor at Faculty of Pharmacy of Paris Saclay University (France). Her research area is focused on the development and preclinical evaluations of nanomedicines for imaging and therapy of cardiovascular diseases. Mariana Varna is a co-author for more than 50 publications.

Abstract

Cyclosporin A (CsA) is a molecule with well-known immunosuppressive properties. As it also acts on the opening of mitochondrial permeability transition pore (mPTP), CsA has been evaluated for ischemic heart diseases (IHD). However, its distribution throughout the body and its physicochemical characteristics strongly limits the use of CsA for intravenous administration. In this context, nanoparticles (NPs) have emerged as an opportunity to circumvent the above-mentioned limitations. We have developed in our laboratory an innovative nanoformulation based on the covalent bond between squalene (Sq) and cyclosporin A to avoid burst release phenomena and increase drug loading. After a thorough characterization of the bioconjugate, we proceeded with a nanoprecipitation in aqueous medium in order to obtain SqCsA NPs of well-defined size. The SqCsA NPs were further characterized using dynamic light scattering (DLS), cryogenic transmission electron microscopy (cryoTEM), and high-performance liquid chromatography (HPLC), and their cytotoxicity was evaluated. As the goal is to employ them for IHD, we evaluated the cardioprotective capacity on two cardiac cell lines. A strong cardioprotective effect was observed on cardiomyoblasts subjected to experimental hypoxia/reoxygenation. Further research is needed in order to understand the mechanisms of action of SqCsA NPs in cells. This new formulation of CsA could pave the way for possible medical application.

Original Article published: Gendron, A.; Lan Linh Tran, N.; Laloy, J.; Brusini, R.; Rachet, A.; Gobeaux, F.; Nicolas, V.; Chaminade, P.; Abreu, S.; Desmaële, D.; Varna M., New Nanoparticle Formulation for Cyclosporin A: In Vitro Assessment. Pharmaceutics 2021, 13, 91.

https://doi.org/10.3390/ pharmaceutics13010091