Comprehensive evaluation of EGFR and AKT targeting efficacy of resveratrol loaded PEGylated liposomes for the glioblastoma management: In silico, in vitro BBB permeation studies.

Red grapes contain resveratrol (Resv), a polyphenol with anti-inflammatory, anti-diabetic, and anticancer properties. In this study, in silico molecular docking was used to assess the binding affinity of Resv to target proteins. Resv was encapsulated in PEGylated liposomes (LNPs) using Phospholipon 90G, cholesterol, and DSPE-mPEG. The particle size, surface charge, and structural details of the Res-LNPs and the Blank LNPs were determined. The effects of Res-LNPs and pure Resv were examined in vitro in C6 (rat glioma) and U87 MG (human glioblastoma) cell lines to evaluate cell survival, uptake, wound healing, and apoptosis. BBB permeability of the Res-LNPs was assessed using an in vitro BBB model with hCMEC/D3 cells. EGFR and AKT 1 and 2 expression levels in Resv-treated U87 MG cells were analyzed by RT-qPCR. Res-LNPs had a particle size of 155.0 ± 1.62 nm and an encapsulation efficiency (% EE) of 76.62 ± 3.43. FTIR, DSC, and XRD analyses confirmed the complete entrapment of Resv within the LNPs, displaying a unilamellar spherical morphology, as verified by SEM and TEM. In vitro studies on C6 and U87 MG cell lines showed that Res-LNPs significantly improved cell viability, uptake, migration, and apoptosis compared with Resv. An in vitro BBB model demonstrated that Res-LNPs efficiently crossed the BBB and accumulated in brain cancer cells. RT-qPCR results indicated that Resv treatment reduced EGFR and AKT 1 and 2 gene expression in U87 MG cells. These results suggest that Res-LNPs effectively crossed BBB and inhibited EGFR and its downstream pathways in glioma cell lines.