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New Nanoparticle Formulation for Cyclosporin A: In Vitro Assessment

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 limit 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.
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https://hal-cea.archives-ouvertes.fr/cea-03119866
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Submitted on : Monday, January 25, 2021 - 10:47:17 AM
Last modification on : Friday, October 29, 2021 - 9:40:02 PM
Long-term archiving on: : Monday, April 26, 2021 - 6:39:22 PM

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Amandine Gendron, Natalie Lan Linh Tran, Julie Laloy, Romain Brusini, Aurélie Rachet, et al.. New Nanoparticle Formulation for Cyclosporin A: In Vitro Assessment. Pharmaceutics, MDPI, 2021, 13 (1), pp.91. ⟨10.3390/pharmaceutics13010091⟩. ⟨cea-03119866⟩

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