Fabrication and optimization of valsartan-loaded transbilosomes for management of diabetes mellitus-accelerated stroke

Abstract

Stroke is the second leading cause of death, particularly among diabetic patients. Valsartan (VST) has the potential to alleviate and prevent strokes due to its antioxidant properties. However, the poor solubility and low bioavailability of VST limit its effectiveness. Therefore, this study aimed to develop a nasal formulation of VST-loaded transbilosomes (VLT) to enhance VST’s efficacy, sustainability, bioavailability, and targeting as a treatment for diabetes mellitus-accelerated stroke (DMAS). The Box-Behnken design was employed for the formulation development and optimization of VLT. An experimental rat model of DMAS was utilized for the in vivo study. The optimal VLT formulation consisted of phospholipid (262.14 mg), Span 60 (20 mg), and sodium deoxycholate (10 mg). When compared to free VST, the optimal VLT formulation improved sustainability, permeability, bioavailability, and targeting of VST by 68.69 %, 7.17-fold, 6.15-fold, and 3.98-fold, respectively. Compared with the positive DMAS control, the optimal VLT group enhanced the neurobehavioral activity of DMAS rats in terms of flexion, spontaneous motor activity, time spent in the target quadrant, and grip strength by 68.52 %, 51.96 %, 83.64 %, and 2.43-fold, respectively. The histopathological study confirmed these results. In conclusion, these findings suggest that the nasal VLT formulation could be a promising therapy to prevent DMAS.