Drug delivery to the spinal cord tagged with nanowire enhances neuroprotective efficacy and functional recovery following trauma to the rat spinal cord.
The possibility that drugs attached to innocuous nanowires enhance their delivery within the central nervous system (CNS) and thereby increase their therapeutic efficacy was examined in a rat model of spinal cord injury (SCI). Three compounds--AP173 (SCI-1), AP713 (SCI-2), and AP364 (SCI-5) (Acure Pharma, Uppsala, Sweden)--were tagged with TiO(2)-based nanowires using standard procedure. Normal compounds were used for comparison. SCI was produced by making a longitudinal incision into the right dorsal horn of the T10-T11 segments under Equithesin anesthesia. The compounds, either alone or tagged with nanowires, were applied topically within 5 to 10 min after SCI. In these rats, behavioral outcome, blood-spinal cord barrier (BSCB) permeability, edema formation, and cell injury were examined at 5 h after injury. Topical application of normal compounds in high quantity (10 microg in 20 microL) attenuated behavioral dysfunction (3 h after trauma), edema formation, and cell injury, as well as reducing BSCB permeability to Evans blue albumin and (131)I. These beneficial effects are most pronounced with AP713 (SCI-2) treatment. Interestingly, when these compounds were administered in identical conditions after tagging with nanowires, their beneficial effects on functional recovery and spinal cord pathology were further enhanced. However, topical administration of nanowires alone did not influence trauma-induced spinal cord pathology or motor functions. Taken together, our results, probably for the first time, indicate that drug delivery and therapeutic efficacy are enhanced when the compounds are administered with nanowires.
Sharma
Hari Shanker
HS
Department of Surgical Sciences, University Hospital, Uppsala University, SE-75421 Uppsala, Sweden. sharma@surgsci.uu.se
Ali
Syed F
SF
Dong
W
W
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; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000295:instrumentation* / Q000379:methods*; D007202:Indicators and Reagents; D008297:Male; D008854:Microscopy, Electron / Q000379:methods; D053770:Nanowires / Q000627:therapeutic use* / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology
D007202:Indicators and Reagents; D018696:Neuroprotective Agents