Transcending Traditional Treatment: The Therapeutical Potential of Nanovesicles for Transdermal Baclofen Delivery in Repeated Traumatic Brain Injury.

PURPOSE

The repositioning of previously approved drugs is occupying the researchers' plans. Baclofen (Bac) was our candidate for its established neuroprotective capacity, with a proposal of efficient drug delivery as non-ionic surfactant-based nanovesicles (NISNV) formulae against mild repetitive traumatic brain injury (mRTBI) in rats, thus reducing the number of orally or injected medications, especially in severely comatose patients or pediatrics.

METHODS

A (2) factorial design was implemented for confining Bac-loaded NISNV formulae, where a bunch of variables were inspected. An experiment was done to test the prepared formula's efficacy transdermally. The following parameters were measured: brain expression of gamma amino butyric acid (GABA), protein kinase C- α (PKC-α), focal adhesion kinase (FAK), TNF-α and nuclear factor kappa B (NF-κB) p65, malondialdehyde (MDA), superoxide dismutase (SOD), and histopathology.

RESULTS

The particle size (PS) and entrapment efficiency percent (EE%) speckled from 60.40±0.28% to 88.02±0.01% for the former and 174.64±0.93 to 1174.50±3.54 nm for the latter. release% after 8 hours ranged from 63.25±5.47% to 84.79±3.75%. The optimized formula (F4) illustrated desirability=1, with 630.09±3.53 µg/cm of Bac permeated over 8 hours, which equates to 100% of Bac. Bac post-trauma treatment restored brain expression of GABA and PKC-α, while decreasing FAK. Besides enhancing the histological findings, the anti-inflammatory effect was clear by decreasing TNF-α and NF-κB p65. Consequently, significant antioxidant sequelae were revealed herein by diminishing MDA levels and restoring SOD activity.

CONCLUSION

Transdermal delivery of Bac-loaded niosomes confirmed neuroprotection and succeeded in surpassing skin-to-brain barriers, which makes it a promising therapeutic option for repeated traumas.