149 Nanoprodrug Accumulates in Experimental Traumatic Brain Injury

We have developed a nanoprodrug that is responsive to oxidative stress and induces release of active nonsteroidal anti-inflammatory drugs in the presence of reactive oxogen species (ROS). Methods Twelve-week-old male C57/Bl6 mice (Jackson Laboratories) were anesthetized using isoflurane, followed by stereotaxic controlled cortical impact (Leica Microsystems Inc.) to the left parietal area at a velocity of 3 m/s, 0.5 ms impact time, 2 mm impact depth, with a 2 mm diameter piston. Mice were then recovered on a warming pad. Five minutes after injury, 18 mice were injected IP with 100 ul of nanoparticle (10 mg/ml) 6 mice were injected IV via the tail vein with 100 ul of nanoparticle, and 6 mice were injected IP with normal saline as a control. At 48 hours after injury, mice underwent behavioral testing (rotorod and open field test) and in vivo bioluminescence imaging (Xenogen) followed by euthanasia and collection of whole brain for confocal microscopy. Results The ibuprofen-containing nanoprodrug is released at high concentrations specifically in the presence of oxidative stress. This “proof-ofconcept” of specific delivery of nanoprodrugs to TBI establishes this novel paradigm as a platform to deliver multiple modalities of brain protection and neural regeneration in TBI.