Development and Evaluation of Simvastatin based Self nano emulsifying drug delivery system for treatment of Alzheimer’s Disease

Abstract Background Alzheimer’s disease (AD) is one of the leading causes of mortality and morbidity across the globe. Its incidences are increasing at an immense rate due to inadequate patient compliance. Hence there is a requirement for a requisite treatment strategy. With the enormous efforts of researchers, they have repurposed the drugs for the management of AD. Simvastatin (SIM) could be one of them. Hence the present work was focused on the formulation development and optimization of self‐nano emulsifying drug delivery system of SIM against AlCl3‐induced AD in rats. Method On the basis of pre‐formulation studies oils, surfactants, and cosurfactants were selected. SNEDDS was prepared by stirring technique in which initial trials were done in the ratio of 1:1, 1:2, and 2:1. Further optimized by Box Behnken design. The developed formulation was further characterized for particle size, zeta potential, PDI, TEM analysis, and drug loading (DL). MTT assay was done using SH‐SY5Y cell lines to evaluate toxicity of the developed formulation. In vivo, the evaluation of the developed formulation was tested on an AlCl3‐induced AD rats model. Result The optimized formulation exhibited P.S, Z.P, PDI, and DL of 57.46±2.65 nm, ‐13.6±1.18 mV, 0.2±0.11 and 88%, respectively. MTT assay confirmed that the prepared formulation was free of toxicity and safe to use for in vivo study. Most importantly, in vivo, administration of SIM‐SNEDDS resulted in significantly increased bioavailability of SIM in the brain compared to the standard drug donepezil (DPZ) and unprocessed SIM. The range of therapeutic efficacy was better in SIM‐SNEDDS high dose followed by SIM‐SNEDDS low dose, and then DPZ and further naïve SIM bioavailability of SIM in the brain compared to the standard drug DPZ and unprocessed SIM. The range of therapeutic efficacy was better in SIM‐SNEDDS high dose followed by SIM‐SNEDDS low dose, and then DPZ and naïve SIM. Conclusion The results of the study concluded that SIM SNEDDS was safe to use in rats. The developed formulation helped in managing AD by promoting antioxidant, anti‐inflammatory and anti‐hyperlipidemic activity. Further explorations with other models and clinical trials are required to better understand the effect of SNEDDS of SIM.