Network Pharmacology and Optimization of β-Sitosterol-Loaded Solid 
Lipid Nanoparticles Using Box-Behnken Design for Enhanced Solubility and Sustained Drug Release in Diabetes

The pharmaceutical industry has paid a lot of attention to solid lipid nanoparticles (SLN) because they show promising drug delivery vehicles.

This work aimed to design and optimize the SLN of β-sitosterol, a hydrophobic drug, to improve solubility and sustained action. An ultrasonication technique after melting was used to design SLN using a randomized response surface Box-Behnken design (BBD). Network pharmacology analysis was performed to explore the interactions between genes. According to the findings, Compritol ATO 888 was the most soluble at a drug: lipid ratio of 1:3. Particle size, PDI, zeta, and entrapment efficiency (EE) were observed as 168.83nm, 0.231 -28.9 Mv, and 68.29%, respectively. The optimized formulation did not undergo any chemical changes, as depicted through DSC. The in vitro drug release investigation showed that the SLN released the drug continuously for 28 hours. Scanning Electron Microscopy (SEM) revealed homogenous, spherical particles.

The antidiabetic potential of the formulation was assessed through the potential of glucose uptake by yeast, and the α-amylase inhibitory assay revealed its significant antidiabetic potential when compared with that of the standard drug metformin. The network pharmacology of β-sitosterol demonstrated gene interaction with hexokinase, phosphoglucomutases, glucose-6-phosphate dehydrogenase, hexose-6-phosphate dehydrogenase, and glutathione disulfide reductase.

The β-sitosterol-loaded SLN generated by BBD was found to be a potential method for improving drug solubility with sustained drug release and was found to be long-term storage stable.