Counteracting Muscle Atrophy on Earth and in Space via Nanofluidics Delivery of Formoterol

Andrea Ballerini, Corrine Ying Xuan Chua, Jessica Rhudy, Antonia Susnjar, Nicola Di Trani, Priya R. Jain, Grit Laue, Danuta Lubicka, Yasaman Shirazi-Fard, Mauro Ferrari, Louis S. Stodieck, Samuel M. Cadena, Alessandro Grattoni

Research output: Contribution to journalArticle

Abstract

Skeletal muscle atrophy is a critical health problem that affects quality of life and increases morbidity and mortality. At present, exercise training remains the only intervention and pharmaceutical treatments remain elusive. Formoterol (FMT), a β2-adrenergic receptor agonist, has emerged as a potential therapeutic by triggering skeletal muscle anabolism with daily dosing. Here, the efficacy of sustained FMT release is investigated via a subcutaneously implanted nanofluidic delivery system (nF) to prevent muscle wasting. Pharmacokinetics of nF-mediated sustained FMT delivery (nF-FMT) in healthy mice is assessed for 56 days, which demonstrates an anabolic effect on skeletal muscles. Using a hind limb suspension unloading mouse model, it is shown that nF-FMT treatment attenuates soleus mass loss in comparison to control mice. Further, the very first study of an implantable drug delivery device in microgravity in vivo is launched. The microgravity environment aboard the International Space Station is leveraged to assess the atrophy prevention capability of nF-FMT in mice for 29 and 55 days. Muscle hypertrophy is observed in both ground control and spaceflight mice treated with nF-FMT compared to their respective vehicle controls. Overall, the nF system is presented as a viable platform for sustained delivery of FMT for therapeutic intervention of skeletal muscle atrophy.

Original languageEnglish (US)
Article number2000014
JournalAdvanced Therapeutics
Volume3
Issue number7
DOIs
StatePublished - Jul 1 2020

Keywords

  • drug delivery
  • implantable devices
  • microgravity
  • muscle atrophy
  • nanofluidics

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, medical
  • Pharmacology (medical)
  • Genetics(clinical)
  • Pharmaceutical Science
  • Pharmacology

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