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 compoundsAP173 (SCI-1), AP713 (SCI-2), and AP364 (SCI-5) (Acure Pharma, Uppsala, Sweden)were tagged with TiO2-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 T10T11 segments under Equithesin anesthesia. The compounds, either alone or tagged with nanowires, were applied topically within 5 to 10min after SCI. In these rats, behavioral outcome, bloodspinal cord barrier (BSCB) permeability, edema formation, and cell injury were examined at 5h after injury. Topical application of normal compounds in high quantity (10?g in 20?L) attenuated behavioral dysfunction (3h after trauma), edema formation, and cell injury, as well as reducing BSCB permeability to Evans blue albumin and 131I. 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.
nanowires spinal cord injury bloodspinal cord barrier evans blue spinal cord edema functional paralysis radioiodine protein tracer spinal cord damage