The prevalence of Parkinson’s disease places a significant burden on society; therefore, there is an urgent need to develop more effective drugs. However, the development of these drugs is both expensive and risky. Quercetin (QUE) has potent pharmacological effects on neurodegenerative diseases, but its low solubility in water and poor bioavailability limit its use in pharmaceutical applications. In this study, Quercetin nanocrystals (QNC) were synthesized and compared to standard QUE. A network-pharmacology-based methodology was applied, including target prediction, network construction, a gene ontology (GO) analysis, a KEGG pathway enrichment analysis, and molecular docking. This study aimed to identify the targets of QUE relevant to the treatment of Parkinson’s disease and investigate the associated pharmacological mechanisms. Most of the predicted targets are involved in dopamine uptake during synaptic transmission. QUE regulates the key targets DRD2 and DRD4, which significantly affect dopaminergic synapses. The molecular docking results showed that QUE had a better binding affinity than the standard drug l-Dopa. From these experiments, it can be concluded that QNC effectively reduced the adverse effects caused by rotenone-induced oxidative stress in biochemical, neurochemical, and histopathological alterations. Therefore, QNC can potentially treat Parkinson’s disease, and its effectiveness should be assessed in future clinical trials.

Solid-lipid nanoparticles (SLNs) are an alternative carrier system used for loading the drug for targeting, improving the bioavailability by increasing its solubility, and protecting the drug from presystemic metabolism. The avoidance of presystemic metabolism is due to the nanometric size range so that the liver cannot uptake the drug from the delivery system and is not metabolized by the liver. Bortezomib is an anti-cancer drug. Due to its poor oral bioavailability, presystemic metabolism and decreased half-life, it was chosen to formulate as the SLN system with the use of a 3-factor, 3-level Box–Behnken design, by hot homogenization followed by an ultrasonication method. Trimyristin (Dynasan-114), tripalmitin (Dynasan 116) and tristearin (Dynasan-118) were used as lipids and based on the results from the initial studies tripalmitin (Dynasan116) was selected as the lipid for the further studies along with phosphatidylcholine as surfactant and Poloxamer 188 as stabilizer. The optimized formulation (F1) was obtained with minimum particle size (204 nm), maximum entrapment efficiency (70.24) and drug loading (21.24). The optimised batches were further investigated by FTIR, DSC, XRD, SEM and stability. In vitro release studies showed that maximum cumulative drug release was obtained for F1 (99.74%). The optimized formulation Bortezomib followed zero-order release kinetics with a strong correlation coefficient (R2= 0.9994). The nanoformulation prepared under optimized conditions is in concurrence with the expected results. It is concluded that the SLN formulation can be used as a potential carrier for the effective delivery of Bortezomib.