Distribution targeting of HIV-1 trans-activator transcription mediated liposomes following spinal cord injury in rats

English Keywords:Spinal cord injury  Liposomes  Spinal cord barrier  Targeting  Rat

English Abstract:

  【Abstract】　Objective：To investigate the in vivo distribution targeting of HIV-1 trans-activator transcription（TAT）-mediated liposomes as drug carriers in rats.Method：HIV-1 TAT-mediated nanoliposome connected with fluorescein isothiocyanate（FITC） acting as a marker were constructed.60 female Wistar rats（8 week） were randomly divided into 2 groups with 30 animals in each group，3 subgroups（n=10） of each group were determined as no damage，24h and 1 week after injury.T10 spinal cord injury models were established by Impactor Model Ⅱ.Group Ⅰ were administed with tail-vein injection of external TAT liposomes（9μg/ml，500μl） at each time point；group Ⅱ with tail-vein injection of liposomes alone（9μg/ml，500μl）.1h after injection，the T7-L1 spinal cord specimen were harvested and observed under dark field microscopy for liposome distribution in spinal cord.Result：FITC-liposomes were observed in the spinal cord in group Ⅰ at 3 time points，but liposomes in intact spinal cord did not enter the neuron.At the time points of 24h and 1 week after injury，liposomes aggregation were noted in injury center inside neurons.24h after injury，FITC fluorescence average optical density（AOD） in neurons liposomes 1.5cm proximal and distal to injury centers were significantly less than in injury center（P<0.05）.While in group Ⅱ，liposomes were not observed in the center of spinal cord injury at preinjury and 1 week after injury，and liposome aggregation were observed in neurons in the center of injury site 24h after injury.AOD at center of injury site 24h after injury showed no significant difference between two groups（P>0.05）.Conclusion：The external TAT liposomes can cross the normal blood and spinal cord barrier，which shows damaged neurons targeting characteristics.