Development and Optimization of Piracetam and Shatavarin IV-Loaded Nanoemulsion for Alzheimer’s Disease Therapy: In Silico and Experimental Analysis

Alzheimer's disease (AD) presents a significant challenge due to cognitive decline resulting from nerve cell degeneration. Shatavarin IV, a prominent bioactive compound from<i>Asparagus racemosus</i> and Piracetam, has been investigated for its neuroprotective potential. This study examines the molecular docking, formulation, and characterization of a nanoemulsion containing Piracetam and Shatavarin IV for treating AD. The <i>in silico</i> study demonstrated that Shatavarin IV exhibited strong binding affinities with multiple AD-related targets, including TNF-α (-7.29 kcal/mol), the GSK-3 axin complex (-9.6785 kcal/mol), amyloid-β (-6.8326 kcal/mol), and GSK-3 β (-8.8243 kcal/mol). The extraction of Shatavarin IV from <i>Asparagus racemosus</i> roots yielded 401.1 ± 2.3 mg with a purity of 66%, as confirmed by HPTLC. A combination index study revealed a synergistic effect with a CI value of 0.10843 at a 1:1 ratio of Piracetam and Shatavarin IV. The nanoemulsion was optimized using a Box-Behnken design, with oil concentration, surfactant mixture (<i>S</i> _mix), and sonication time as key factors. The optimized formulation exhibited a particle size of 183.6 nm and a PDI of 0.194. Characterization techniques, including TEM and DSC, confirmed the uniformity, stability, and incorporation of the drugs in the nanoemulsion. The <i>in vitro</i> drug release study revealed a significantly higher release profile (84.30 ± 1.03% in 24 h) for the nanoemulsion than the drug suspension. <i>Ex vivo</i> studies demonstrated a superior permeability rate for the nanoemulsion (56.35 ± 1.19%) compared to the conventional suspension. Additionally, the nanoemulsion showed enhanced antioxidant activity compared with the pure extract. Stability studies indicated that the formulation remained stable with only minor changes in particle size, PDI, and zeta potential over time. This nanoemulsion presents a promising therapeutic strategy for AD.