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

Paranthaman Sathishbabu; Chinnappa A Uthaiah; Umme Hani

doi:10.1016/j.bioorg.2024.108077

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

Bioorg Chem. 2024 Dec 19:154:108077. doi: 10.1016/j.bioorg.2024.108077. Online ahead of print.

Authors

Paranthaman Sathishbabu¹, Chinnappa A Uthaiah², Umme Hani³

Affiliations

¹ Department of Cell Biology and Molecular Genetics, Sri Devaraj Urs Medical College, Sri Devaraj Urs Academy of Higher Education and Research, Kolar, Tamaka 563103, Karnataka, India; Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru 570015, Karnataka, India. Electronic address: sathishbabu.p94@gmail.com.
² Centre of Excellence in Molecular Biology and Regenerative Medicine (CEMR) Laboratory, (a DST-FIST Sponsored Centre) Department of Biochemistry (a DST-FIST Sponsored Department), JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER), Mysuru 570015, Karnataka, India.
³ Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia.

PMID: 39718077
DOI: 10.1016/j.bioorg.2024.108077

Abstract

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-mPEG₂₀₀₀. 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.

Keywords: Anti-cancer activity; Epidermal growth factor receptor; Glioma; Liposomes; Resveratrol.