In-Silico Evaluation and Development of a Nanoemulsion System of Withania somnifera Phytoconstituents for Multi-target Intervention in Alzheimer’s Disease

¹ Department of Biotechnology, Jaypee Institute of Information Technology, Noida, U.P., India
² Indian Institute of Technology Bombay Monash Research Academy, Mumbai, India
³ Faculty of Health, Graduate School of Health, University of Technology Sydney, Australia
⁴ Woolcock Institute of Medical Research, University of Sydney, Sydney, Australia

^* Corresponding author: This email address is being protected from spambots. You need JavaScript enabled to view it.

Abstract

Neurodegenerative diseases, especially AD, is becoming a worldwide health burden with characteristic features such as neuronal loss, synaptic impairments, progressive degeneration of neocortex and aggregation of amyloid (P). Current drugs used to treat Neurodegenerative diseases merely offer symptom relief and do not alter disease course owing to poor BB barrier (BBB) permeability and poor pharmacokinetics. Nanotherapeutics are thus being investigated as potential tools to improve specific delivery of compounds to the brain. In this study the neuroprotective efficacy of Withania somnifera extract-loaded nano-emulsion systems has been demonstrated through interaction of several molecular targets involved in AD. The in silico molecular docking studies clearly established significant binding energy of the investigated bioactives (withanolides, withaferin A, quercetin, L, ascorbic acid etc,) towards major therapeutic targets involving AD (AChE, BChE, NMDA receptor, BACE1, MAO, A, ApoE) and so indicate their significant activity against multi targets of AD. Different oils, surfactants and co, surfactants were chosen and studied for extract solubilization for nano-emulsion formation. Almond oil, triacetin and ethanol were selected based on solubilization for formulation development adopting water titration method. A water titration employing Smix (surfactant and co, surfactant) of 2:1 ratio led to the formation of stable oil, in, water nano, emulsion system. The developed formulations showed physicochemical parameters within acceptable limits: PH (3.74, 4.20), conductivity (61.3, 86.8 m S/m), viscosity (34.3, 41.1 c P) and density (0.964 g/m L). Dynamic light scattering particle size analyser revealed average particle sizes from 185.5 to 212 nm, with value of zeta potential between 28 and 33 mV. Spherical structures within the nanometric range were confirmed using transmission electron microscopy, and extract encapsulation was detected using FTIR. In general, the nanoemulsion loaded with produced here showed adequate physicochemical stability and ability to target multiple pathologies. Further, we need to do pharmacokinetic and pharmacodynamic studies in order to determine therapeutic effects in the brain.