Intranasal Delivery of miR133b in a NEO100-Based Formulation Induces a Healing Response in Spinal Cord-Injured Mice

Despite important advances in the pre-clinical animal studies investigating the neuroinhibitory microenvironment at the injury site, traumatic injury to the spinal cord remains a major problem with no concrete response. Here, we examined whether (1) intranasal (IN) administration of miR133b/Ago2 can reach the injury site and achieve a therapeutic effect and (2) NEO100-based formulation of miR133b/Ago2 can improve effectiveness. 24 h after a cervical contusion, C57BL6 female mice received IN delivery of miR133b/Ago2 or miR133b/Ago2/NEO100 for 3 days, one dose per day. The pharmacokinetics of miR133b in the spinal cord lesion was determined by RT-qPCR. The role of IN delivery of miR133b on motor function was assessed by the grip strength meter (GSM) and hanging tasks. The activity of miR133b at the lesion site was established by immunostaining of fibronectin 1 (FN1), a miR133b target. We found that IN delivery of miR133b/Ago2 (1) reaches the lesion scar and co-administration of miR133b with NEO100 facilitated the cellular uptake; (2) enhanced the motor function and addition of NEO100 potentiated this effect and (3) targeted FN1 expression at the lesion scar. Our results suggest a high efficacy of IN delivery of miR133b/Ago2 to the injured spinal cord that translates to improved healing with NEO100 further potentiating this effect.

Automated summary

This study aimed to investigate whether intranasal administration of miR133b/Ago2 can reach the injury site and have a therapeutic effect, and whether the addition of NEO100-based formulation can improve effectiveness. The results showed that miR133b/Ago2 can reach the lesion scar through intranasal delivery, and co-administration with NEO100 facilitated cellular uptake, improved motor function, and targeted FN1 expression at the lesion scar. These findings suggest that intranasal delivery of miR133b/Ago2 can effectively treat spinal cord injury, and NEO100 can enhance this therapeutic effect.