Jian Li, Jun Wei, Yujie Wan
May 17, 2021
Citations
0
Influential Citations
21
Citations
Quality indicators
Journal
Journal of controlled release : official journal of the Controlled Release Society
Abstract
Tetramethylpyrazine (TMP) has been effectively used for treating spinal cord injury (SCI) due to its anti-inflammatory, antioxidant, and neuroprotective activity. However, its clinical application is limited due to poor water solubility and insufficient spinal cord targeting through the traditional dosage forms. Given that intravascular neutrophils are quickly recruited to the injury site as part of the inflammatory response in SCI, we conjugated the cell-penetrating HIV trans-activator of transcription (TAT) peptide to human serum albumin nanoparticles (NPs) to make a TMP delivery system (TAT-TMP-NPs) that could be internalized by neutrophils and delivered to SCI lesions. Results found that in SCI rats TAT-TMP-NPs promoted the recovery of locomotor function and the lesion area, while reducing the levels of inflammatory cytokines and oxidative stress-related factors. Safety evaluation and in vivo small-animal imaging showed that the cell-penetrating peptide TAT could enhance the uptake of TAT-TMP-NPs by neutrophils without being toxic to the body. TAT-TMP-NPs may overcome the poor water solubility and low bioavailability of TMP, showing promise for the clinical treatment of SCI.