Antioxidant and Neuroprotective Capacity of Resveratrol-Loaded Polymeric Micelles in In Vitro and In Vivo Models with Generated Oxidative Stress

<b>Background</b>: Resveratrol (3,5,4'-trihydroxy-trans-stilbene, RVT) is one of the most extensively studied natural polyphenols, with numerous health benefits documented in the literature. One of its most characterized biological properties is the strong antioxidant capacity. However, its poor biopharmaceutical properties limit its in vivo applicability. In this study, we conducted a detailed comparative analysis of the antioxidant and protective capacity of pure and loaded into Pluronic micelles resveratrol. <b>Methods</b>: Various in vitro antioxidant assays, such as DPPH, ABTS, superoxide anion radical scavenging, ferric (FRAP), and copper-reducing power assay (CUPPRAC), and iron-induced lipid peroxidation were performed. In addition, the in vitro 6-OHDA model of neurotoxicity in brain synaptosomes and the in vivo scopolamine (Sco)-induced model of cognitive impairment in rats were also employed. The main antioxidant biomarkers-the levels of lipid peroxidation (LPO) and total glutathione (GSH), as well as activities of superoxide dismutase, catalase, and glutathione peroxidase-were measured in the cortex and hippocampus. <b>Results</b>: The results from the in vitro tests demonstrated better ferric-reducing power activity and better neuroprotective capacity of the micellar resveratrol (mRVT), as evidenced by preserved synaptosomal viability and maintained GSH levels in a concentration-dependent manner in 6-OHDA-induced neurotoxicity. Regarding the in vivo results, mRVT (10 µM concentration) was the most effective treatment in supporting recognition memory formation in dementia rats. Further, mRVT demonstrated better LPO protective capacity in the hippocampus and GSH preserving activity in the cortex than the pure drug. <b>Conclusions</b>: The incorporation of resveratrol in polymeric micelles could enhance its antioxidant and neuroprotective effects.