## 4 Discussion  
The present research explored the cytoprotective, genoprotective, and antioxidant capacities of resveratrol-loaded Pluronic (P123/F127) micelles as an approach to improve the low water solubility and poor bioavailability of pure resveratrol. The in vitro effects of mRVT (an aqueous dispersion) were compared with those of pure RVT (30% hydroethanolic solution) in the human U87 MG glioblastoma cell line with H\({}_{2}\)O\({}_{2}\)-induced oxidative damage. Oxidative stress as an imbalance in ROS generation and deactivation has been linked to several neurodegenerative diseases [3; 7; 8; 49; 50]. The central nervous system (CNS) is especially susceptible to oxidative damage because of its elevated oxygen consumption, weak antioxidant defenses, and limited capacity for cellular regeneration [8; 14]. Antioxidants of natural origin have been proposed as preventive and therapeutic agents for neurodegenerative diseases due to their potential to mitigate oxidative stress-induced damage in neuronal cells [16; 50; 51; 52; 53; 54; 55; 56; 57]. RVT is a natural polyphenol known for its diverse pharmacological properties, including significant antioxidant activity [22; 23]. Its low bioavailability poses significant challenges for clinical use and one possible way to address this limitation is encapsulation of resveratrol in polymeric nanomicelles as a drug delivery system. As the first step in our research, the cellular internalization of rhodamine-B-marked Pluronic (P123/F127) micelles was evaluated. As shown in Figure 7, the obtained morphological alterations of the cells demonstrate that the rhodamine-B-loaded micelles were localized in the cytoplasm 1 h after treatment. As the next step cytotoxicity of empty micelles (in the range of 0.2-30 \(\upmu\)g/mL), RVT and mRVT (in the range of 1 to 30 \(\upmu\)M) was assessed in human U87 MG glioblastoma cells via an MTT assay. Our results showed that 24 h incubation with empty micelles, RVT, and mRVT caused no significant changes in cell viability, indicating a lack of toxicity. This is consistent with previous findings showing that several hours of incubation with RVT at concentrations below 50 \(\upmu\)M does not cause cell toxicity in PC12 cells [58; 25]. The lack of toxicity of P123/F127 micelles loaded with cannabidiol in SH-SYSY and Neuro-2a cells line was also reported [41]. H\({}_{2}\)O\({}_{2}\) is a major redox-signaling molecule in cells under physiological conditions and widely used to induce oxidative stress-related damage, particularly in neuronal cell models at supraphysiological concentrations [5; 59; 60; 61; 62]. Due to its small size and neutral charge, H\({}_{2}\)O\({}_{2}\) easily crosses cell membranes and contributes to the generation of highly reactive  
Figure 7: The fluorescence microscopic images of U87 MG cells; (**a–c**) non-treated (control group) and (**d–f**) incubated with rhodamine B-loaded micelles for 1 h. Nuclei were stained with DAPI (blue), cells incubated with rhodamine-B micelles (red), and the two images were merged. Objective 40 \(\times\). hydroxyl radicals through [PERSON]'s reaction. The byproducts of this reaction, along with H2O2 itself, can directly interact with cellular macromolecules, including proteins, lipids, and DNA [63]. These changes in cellular metabolism can potentially lead to cell death through apoptosis [64; 65; 66; 67; 68; 69]. In this study, H2O2 at cytotoxic concentration of 200 uM [70] was used to create a model of oxidative stress-induced cell damage where the protective effects of RVT and mRVT were compared after 24 h of preincubation. Under our experimental conditions, both the pure and encapsulated forms of resveratrol reversed the cytotoxic effects of H2O2 at all tested concentrations. However, mRVT at low concentrations (1 and 3 uM) was more effective than the pure drug at equivalent concentrations.