Nanowired-drug delivery enhances neuroprotective efficacy of compounds and reduces spinal cord edema formation and improves functional outcome following spinal cord injury in the rat.
The possibility that drugs attached to nanowires enhance their therapeutic efficacy was examined in a rat model of spinal cord injury (SCI). Three Acure compounds AP-173, AP-713 and AP-364 were tagged with TiO(2)-based nanowires (50-60 nm) and applied over the traumatized cord either 5 or 60 min after SCI in rats produced by a longitudinal incision into the right dorsal horn of the T10-11 segments under equithesin anaesthesia. Normal compounds were used for comparison. After 5 h SCI, behavioral outcome, blood-spinal cord barrier (BSCB) permeability, edema formation and cell injury were examined. Topical application of nanowired compound AP-713 (10 microg in 20 microL) when applied either 5 or 60 min after injury markedly attenuated behavioral dysfunction at 2-3 h after SCI and reduces BSCB disruption, edema formation and cord pathology at 5 h compared to other compounds. Whereas normal compounds applied at 5 min after injury (but not after 60 min) had some significant but less beneficial effects compared to their nanowired combinations. On the other hand, nanowires alone did not influence spinal cord pathology or motor function after SCI. Taken together, our results indicate that the nanowired-drug-delivery enhances the neuroprotective efficacy of drugs in SCI and reduces functional outcome compared to normal compounds even applied at a later stage following trauma, not reported earlier.
Sharma
Hari Shanker
HS
Laboratory of Cerebrovascular Research, Department of Surgical Sciences, Anaesthesiology and Intensive Care Medicine, University Hospital, Uppsala, Sweden. Sharma@surgsci.uu.se
Ali
Syed F
SF
Tian
Z Ryan
ZR
Patnaik
R
R
Patnaik
S
S
Sharma
Aruna
A
Boman
Arne
A
Lek
Per
P
Seifert
Elisabeth
E
Lundstedt
Torbjörn
T
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D004487:Edema / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D046529:Microscopy, Electron, Transmission / Q000379:methods; D053770:Nanowires / Q000008:administration & dosage*; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy; D013997:Time Factors
D018696:Neuroprotective Agents