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 of ten caused eleteriousside 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.