Tabriz University of Medical Sciences Advanced Pharmaceutical Bulletin 2228-5881 16 3 2026 09 30 Enhancing Apoptosis in Glioblastoma Through Hybrid Nanoparticle-Mediated Resveratrol Delivery: In Vitro Cytotoxicity and in Vivo Pharmacokinetic Study 573 582 10.34172/apb.46117 EN Swati Devendra Raysing https://orcid.org/0000-0002-2114-8560 Ashish Prakash Gorle Journal Article 10.34172/apb.46117 2025 08 02 2026 03 21 Introduction: Glioblastoma multiforme (GBM) is the most prevalent malignant primary brain tumor of the central nervous system (CNS), with limited therapeutic success due to challenges such as the blood-brain barrier and poor drug bioavailability. Resveratrol (RSV), a natural polyphenol with known anticancer activity, shows promise against GBM but suffers from low systemic absorption and limited brain targeting. This study investigates the therapeutic potential of RSV-loaded lipopolymeric hybrid nanoparticles (RSV-LPHNs) as a novel delivery platform to enhance RSV’s efficacy in GBM treatment. Methods: This study evaluated the anticancer and targeting efficiency of RSV-LPHNs through a series of in vitro and in vivo assays. The potential of RSV-LPHNs against GBM was investigated by assessing Cellular Apoptosis, ROS Estimation, cell cycle kinetics, MMP Estimation with Flow Cytometry- U87 and DNA Fragmentation Assay. Furthermore, in vivo pharmacokinetic studies in rat were performed followed by brain distribution study. Results: In U87 glioblastoma cells, RSV-LPHNs induced apoptosis via increased reactive oxygen species (ROS) production and disrupted mitochondrial membrane potential (MMP), confirmed by flow cytometry. In vivo pharmacokinetic studies in rats showed that RSV-LPHNs achieved a significantly higher AUC (0–∞) (94.58 µg•h/mL) compared to plain RSV (10.68 µg•h/mL), resulting in a 3.77-fold improvement in relative bioavailability. Brain distribution studies demonstrated a notable increase in brain AUC, from 7.11 to 47.20 µg•h/mL, indicating a 2.28-fold enhancement in brain. Conclusion: By improving RSV’s cellular uptake, apoptotic effect, and brain delivery, RSV-LPHNs may represent a viable and effective neurotherapeutic platform for combating glioblastoma multiforme.