Formulation and optimization of metformin-berberine loaded solid lipid nanoparticles for their neuroprotective effects in the brain

Background: The increasing prevalence of Type 2 Diabetes Mellitus (T2DM) is associated with a heightened risk of developing Alzheimer’s Disease (AD), highlighting the need for effective therapeutic strategies that address the shared pathophysiological mechanisms in both conditions. Methodology: The Metformin-Berberine loaded solid lipid particles (MBSLNs) were prepared by dispersion of different concentrations of stearic acid, polysorbate 80, poloxamer 407, sesame oil, metformin, and berberine. Factor screening studies have been done to identify the influential components. An optimization study was then conducted using a three-factor Box-Behnken design with Design-Expert software. In-Vivo studies confirmed the neuroprotective role of SLNs. Results: The optimized concentrations of the variable factors were determined using the overlay plot generated by the software, resulting in stearic acid (4.84%), polysorbate 80 (1.50%), Poloxamer 407 (1%), and sesame oil (0.31%). The responses, particle size (10–200 nm), zeta potential (> ±30 mV), and polydispersity index (PDI) (0–1) were achieved within the desired range. Discussion: The closeness in experimental and predicted values confirms the reliability of the optimization technique. The optimized formulation exhibits a significant reduction in oxidative stress, and decreased glucose levels were observed when compared to the control, indicating a neuroprotective effect of the formulation. Conclusion: The optimized MBSLNs were affected by the independent parameters examined, including stearic acid, polysorbate 80, Poloxamer 407, and sesame oil concentrations, with significant effects on particle size, zeta potential, and size distribution. The utilization of MBSLNs has emerged as a remarkably effective strategy for enhancing the biological activity of Metformin and berberine in treating T2DM-induced AD.