L-Carnitine Functionalization to Increase Skeletal Muscle Tropism of PLGA Nanoparticles |
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Authors: | Ilaria Andreana Manuela Malatesta Maria Assunta Lacavalla Federico Boschi Paola Milla Valeria Bincoletto Carlo Pellicciari Silvia Arpicco Barbara Stella |
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Affiliation: | 1.Department of Drug Science and Technology, University of Torino, I-10125 Torino, Italy;2.Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, I-37134 Verona, Italy;3.Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, I-27100 Pavia, Italy;4.Department of Computer Science, University of Verona, I-37134 Verona, Italy |
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Abstract: | Muscular dystrophies are a group of rare genetic pathologies, encompassing a variety of clinical phenotypes and mechanisms of disease. Several compounds have been proposed to treat compromised muscles, but it is known that pharmacokinetics and pharmacodynamics problems could occur. To solve these issues, it has been suggested that nanocarriers could be used to allow controlled and targeted drug release. Therefore, the aim of this study was to prepare actively targeted poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) for the treatment of muscular pathologies. By taking advantage of the high affinity for carnitine of skeletal muscle cells due to the expression of Na+-coupled carnitine transporter (OCTN), NPs have been actively targeted via association to an amphiphilic derivative of L-carnitine. Furthermore, pentamidine, an old drug repurposed for its positive effects on myotonic dystrophy type I, was incorporated into NPs. We obtained monodispersed targeted NPs, with a mean diameter of about 100 nm and a negative zeta potential. To assess the targeting ability of the NPs, cell uptake studies were performed on C2C12 myoblasts and myotubes using confocal and transmission electron microscopy. The results showed an increased uptake of carnitine-functionalized NPs compared to nontargeted carriers in myotubes, which was probably due to the interaction with OCTN receptors occurring in large amounts in these differentiated muscle cells. |
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Keywords: | PLGA L-carnitine nanoparticles active targeting skeletal muscle cells fluorescence microscopy transmission electron microscopy |
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