(198u) Targeted Delivery of a Drug Coupled Gold Nanoconjugate Induces Respiratory Recovery Following Cervical Spinal Cord Injury in Rats

Authors: 
Liu, F., Wayne State University
Buttry, J., Wayne State University
Minic, Z., Wayne State University
Goshgarian, H. G., Wayne State University
Mao, G., Wayne State University
The gold nanoconjugates consists of a spherical gold nanoparticle drug carrier chemically conjugated to methylxanthine drugs, and a targeting protein (wheat germ agglutinin coupled to horseradish peroxidase or WGA-HRP). In this poster, we demonstrated a strategy of selectively targeting the lower motor (phrenic) and pre-motor rostral ventral respiratory group (rVRG) neurons responsible for diaphragmatic function in rats by showing persistent respiratory recovery 48 hours after a single intradiaphragmatic injection of the nanoconjugate at 0.1% of free drug dosage inducing therapeutic effect. Biodistribution study was conducted by determining the amount of gold in the blood, RES organs, and targeted tissues after injection. Inductively coupled plasma mass spectrometry was used in this study. The targeted transportation was also demonstrated by anti-WGA immunohistochemical analysis. Respiratory recovery data will include electromyography (EMG) analysis, phrenic nerve recordings, and whole body plethysmography (WBP) on a validated animal model. We also carried out in-vitro drug release studies by monitoring drug released from the nanoconjugates incubated in buffers mimicking different circumstances for time periods ranging from 1 hour to 4 weeks by LC-MS/MS. To conclude, a single administration of the nanoconjugate restored 75% of the respiratory drive at 0.1% of the effective systemic drug dose. This work has important translational implications.