title: Transporter Protein-Coupled DPCPX Nanoconjugates Induce Diaphragmatic Recovery after SCI by Blocking Adenosine A1 Receptors.
abstract: Respiratory complications in patients with spinal cord injury (SCI) are common and have a negative impact on the quality of patients' lives. Systemic administration of drugs that improve respiratory function often cause deleterious side effects. The present study examines the applicability of a novel nanotechnology-based drug delivery system, which induces recovery of diaphragm function after SCI in the adult rat model. We developed a protein-coupled nanoconjugate to selectively deliver by transsynaptic transport small therapeutic amounts of an A1 adenosine receptor antagonist to the respiratory centers. A single administration of the nanoconjugate restored 75% of the respiratory drive at 0.1% of the systemic therapeutic drug dose. The reduction of the systemic dose may obviate the side effects. The recovery lasted for 4 weeks (the longest period studied). These findings have translational implications for patients with respiratory dysfunction after SCI.
  
  
  CONCLUSIONS
  The leading causes of death in humans following SCI are respiratory complications secondary to paralysis of respiratory muscles. Systemic administration of methylxantines improves respiratory function but also leads to the development of deleterious side effects due to actions of the drug on nonrespiratory sites. The importance of the present study lies in the novel drug delivery approach that uses nanotechnology to selectively deliver recovery-inducing drugs to the respiratory centers exclusively. This strategy allows for a reduction in the therapeutic drug dose, which may reduce harmful side effects and markedly improve the quality of life for SCI patients.
authors.affiliation: Wayne State University School of Medicine, Department of Anatomy and Cell Biology, Detroit, Michigan 48201, and.
authors.forename: Zeljka
authors.initials: Z
authors.lastname: Minic
authors.affiliation: Wayne State University College of Engineering, Department of Chemical Engineering and Materials Science, Detroit, Michigan 48202.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Wayne State University College of Engineering, Department of Chemical Engineering and Materials Science, Detroit, Michigan 48202.
authors.forename: Guangzhao
authors.initials: G
authors.lastname: Mao
authors.affiliation: Wayne State University School of Medicine, Department of Anatomy and Cell Biology, Detroit, Michigan 48201, and hgoshgar@med.wayne.edu.
authors.forename: Harry G
authors.identifier: http://orcid.org/0000-0002-5736-3940
authors.initials: HG
authors.lastname: Goshgarian
mesh_terms: D058916:Adenosine A1 Receptor Antagonists / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D003964:Diaphragm / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D053580:Muscle Strength / Q000187:drug effects; D058726:Nanoconjugates / Q000008:administration & dosage / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D020127:Recovery of Function / Q000187:drug effects; D015656:Respiratory Mechanics / Q000187:drug effects; D012133:Respiratory Paralysis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D016896:Treatment Outcome; D018998:Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate / Q000737:chemistry / Q000493:pharmacokinetics; D014970:Xanthines / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D058726:Nanoconjugates; D043682:Receptor, Adenosine A1; D018998:Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate; D014970:Xanthines; C051360:1,3-dipropyl-8-cyclopentylxanthine
keywords: motor systems; nanotechnology; phrenic nucleus; plasticity; respiratory recovery; spinal cord injury