Development, optimization, and evaluation of Empagliflozin nanoemulsion for the management of neuroinflammation associated Alzheimer's disease

Alzheimer's disease (AD) is one of the most pervasive and progressive neurodegenerative disorders. Recently, empagliflozin (EMPA) has been reported as a potent anti-inflammatory and antioxidant in neuroinflammatory disorders apart from antidiabetic activity. To use EMPA for neuroinflammation-associated AD, EMPA must first cross blood–brain barrier (BBB). Hence, an optimized EMPA-nanoemulsion (EMPA-NE) was formulated by applying Box–Behnken experimental design (BBD) approach. The focus of this investigation was to develop, optimize, and evaluate EMPA-NE for the management of neuroinflammation-associated AD. The experimental EMPA-NE had a particle size of 136.1 nm, 0.281 PDI, and zeta potential of −23.9 mV. The lower viscosity of optimized NE showed its usefulness for oral administration. The dispersibility and thermodynamic analysis showed NE stability under different environmental conditions. The release study demonstrated steady, regulated drug release after initial fast drug release from NE. In addition, a stability study of optimized EMPA-NE showed no notable changes in drug content, particle sizes, PDI, and zeta potential. Histopathological estimation showed cells with normal characteristics in EMPA-NE-treated group versus the EMPA-treated group. Antioxidant studies demonstrated a significant increment of SOD (p < 0.001), and CAT (p < 0.001) levels, and a reduction in MDA content (p < 0.001) and effective reversal of high AchE levels (p < 0.001) was also found in EMPA-NE-treated group as compared to LPS treated group. Treatment with EMPA-NE caused a marked reduction in Iba1 molecule and GFAP expression levels, thus demonstrating the anti-inflammatory and neuroprotective potency of EMPA-NE. Therefore, this study reveals promising antioxidant and anti-inflammatory properties of EMPA-NE, which could provide an effective approach to the management of neuroinflammation-associated AD.