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  3. Repurposing pentamidine using hyaluronic acid-based nanocarriers for skeletal muscle treatment in myotonic dystrophy

Repurposing pentamidine using hyaluronic acid-based nanocarriers for skeletal muscle treatment in myotonic dystrophy

  • Nanomedicine. 2022 Oct 26;47:102623. doi: 10.1016/j.nano.2022.102623.
Mathieu Repellin 1,  Flavia Carton 2,  Federico Boschi 3,  Mirco Galiè 2,  Massimiliano Perduca 4,  Laura Calderan 2,  Arnaud Jacquier 5,  Julien Carras 5,  Laurent Schaeffer 5,  Stéphanie Briançon 6,  Giovanna Lollo 6,  Manuela Malatesta 7
Affiliations

Affiliations

  • 1 Department of Neurosciences, Biomedicine and Movement Sciences, Anatomy and Histology Section, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy; University of Lyon, Université Claude Bernard Lyon 1, CNRS, LAGEPP UMR 5007, 43 bd 11 Novembre 1918, 69622 Villeurbanne, France.
  • 2 Department of Neurosciences, Biomedicine and Movement Sciences, Anatomy and Histology Section, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy.
  • 3 Department of Computer Science, University of Verona, Strada Le Grazie 15, 37134 Verona, Italy.
  • 4 Department of Biotechnology, Biocrystallography and Nanostructure Laboratory, University of Verona, Strada Le Grazie 15, 37134 Verona, Italy.
  • 5 Institut NeuroMyogène, University of Lyon1, CNRS UMR 5310, INSERM U1217, 8 avenue Rockefeller, 69008 Lyon, France; Centre de Biotechnologie Cellulaire, CBC Biotec, CHU de Lyon - Hospices civils de Lyon groupement Est, Bron, France.
  • 6 University of Lyon, Université Claude Bernard Lyon 1, CNRS, LAGEPP UMR 5007, 43 bd 11 Novembre 1918, 69622 Villeurbanne, France.
  • 7 Department of Neurosciences, Biomedicine and Movement Sciences, Anatomy and Histology Section, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy. Electronic address: manuela.malatesta@univr.it.
PMID: 36309185 DOI: 10.1016/j.nano.2022.102623
Abstract

In a context of drug repurposing, pentamidine (PTM), an FDA-approved antiparasitic drug, has been proposed to reverse the splicing defects associated in myotonic dystrophy type 1 (DM1). However, clinical use of PTM is hinder by substantial toxicity, leading to find alternative delivery strategies. In this work we proposed hyaluronic acid-based nanoparticles as a novel encapsulation strategy to efficiently deliver PTM to skeletal muscles cells. In vitro studies on C2C12 myoblasts and myotubes showed an efficient nanoparticles' internalization with minimal toxicity. More interestingly, our findings evidenced for the first time the endosomal escape of hyaluronic acid-based nanocarriers. Ex vivo studies showed an efficient nanoparticles' internalization within skeletal muscle fibers. Finally, the therapeutic efficacy of PTM-loaded nanosystems to reduce the number of nuclear foci has been demonstrated in a novel DM1 in vitro model. So far, current data demonstrated the potency of hyaluronic acid-based nanosystems as efficient nanocarrier for delivering PTM into skeletal muscle and mitigate DM1 pathology.

Keywords

Biomaterials; C2C12 cells; DM1 cell model; Muscular dystrophies; Nanoparticles.

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