Synthesis and characterization of berberine-loaded nanoliposome for targeting of MAPK pathway to induce apoptosis and suppression of autophagy in glioblastoma

Abstract

Glioblastoma (GBM), the most aggressive and lethal primary brain tumor, demands innovative therapeutic strategies to improve patient outcomes and quality of life. Addressing this urgent need, our study focuses on developing a berberine (BBR)-loaded nanoliposome (NL) as a targeted drug delivery system to combat GBM. Synthesized using the thin film hydration method and characterized through advanced physical and spectroscopic techniques, these NLs demonstrate promising potential in enhancing BBR's therapeutic efficacy. The NL formulation achieved an impressive loading efficiency of 65.71 ± 1.31% with a particle size of 83 ± 12 nm, ensuring optimal delivery. Sustained release experiments revealed that 82.65 ± 1.75% of the encapsulated BBR was consistently released over 48 h, highlighting its controlled release capabilities.In vitroassays, including cell viability, TUNEL, and western blot analysis, confirmed the potent anti-cancer effects of NL-BBR. The formulation significantly disrupted the metabolism of U-87 glioblastoma cells, inducing enhanced autophagy and apoptosis, ultimately leading to cell death via intrinsic apoptotic pathways. Additionally, western blot results demonstrated that NL-BBR effectively suppressed the mitogen-activated protein kinase signaling pathway, a critical driver of GBM progression. This study underscores the transformative potential of incorporating BBR into NLs, which not only enhances its solubility and bioavailability but also significantly amplifies its therapeutic impact. These findings pave the way for advanced nano-based interventions in GBM treatment, offering a glimmer of hope for improved outcomes in this challenging cancer landscape.

Keywords: MAPK; MTT; apoptosis; autophagy; glioblastoma; hemolysis; in-vitro release.