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Journal Articles Materials Year : 2023

Development and Characterization of Innovative Multidrug Nanoformulation for Cardiac Therapy

Abstract

For several decades, various peptides have been under investigation to prevent ischemia/reperfusion (I/R) injury, including cyclosporin A (CsA) and Elamipretide. Therapeutic peptides are currently gaining momentum as they have many advantages over small molecules, such as better selectivity and lower toxicity. However, their rapid degradation in the bloodstream is a major drawback that limits their clinical use, due to their low concentration at the site of action. To overcome these limitations, we have developed new bioconjugates of Elamipretide by covalent coupling with polyisoprenoid lipids, such as squalenic acid or solanesol, embedding self-assembling ability. The resulting bioconjugates were co-nanoprecipitated with CsA squalene bioconjugate to form Elamipretide decorated nanoparticles (NPs). The subsequent composite NPs were characterized with respect to mean diameter, zeta potential, and surface composition by Dynamic Light Scattering (DLS), Cryogenic Transmission Electron Microscopy (CryoTEM) and X-ray Photoelectron Spectrometry (XPS). Further, these multidrug NPs were found to have less than 20% cytotoxicity on two cardiac cell lines even at high concentrations, while maintaining an antioxidant capacity. These multidrug NPs could be considered for further investigations as an approach to target two important pathways involved in the development of cardiac I/R lesions.

Dates and versions

cea-04065943 , version 1 (12-04-2023)

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Amandine Gendron, Séverine Domenichini, Sandrine Zanna, Frédéric Gobeaux, Christophe Piesse, et al.. Development and Characterization of Innovative Multidrug Nanoformulation for Cardiac Therapy. Materials, 2023, 16 (5), pp.1812. ⟨10.3390/ma16051812⟩. ⟨cea-04065943⟩
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