Objective: Glioblastoma (GBM) remains difficult to treat due to its cellular heterogeneity, diffuse invasion, and the restrictive blood–brain barrier (BBB), all of which limiting drug efficacy. Cannabidiol (CBD), a phytocannabinoid with antitumor, anti-inflammatory, and antioxidant activities, has poor solubility and limited brain penetration. This study aimed to synthesize and characterize cannabidiol-loaded nanoliposomes (CBD-NLs) and evaluate their therapeutic effects in an orthotopic C6 glioma rat model compared with free CBD.
Materials and methods: CBD-NLs were prepared by thin-film hydration and characterized by SEM, TEM, DLS, and FTIR. Adult male Wistar rats (n = 28) were randomized into four groups (n = 7 each): healthy control, glioma model (untreated), free-CBD, and CBD-NL. Endpoints included histopathology (H&E and Cresyl Violet), apoptosis, antioxidant status (Superoxide dismutase (SOD) activity; malondialdehyde (MDA) level, and relative mRNA expression of TNF-α, IL-6, RIPK3, and VDAC1 by RT-qPCR (ΔΔCt).
Results: CBD-NLs formed nearly spherical vesicles (~48.6 nm). FTIR confirmed characteristic phospholipid and CBD functional groups, indicating successful non-covalent incorporation of CBD without chemical degradation. Both CBD and CBD-NL improved tumor histology, increased apoptosis, normalized redox status (increased SOD and decreased MDA), and downregulated TNF-α, IL-6, RIPK3, and VDAC1 (vs. glioma model). Notably, CBD-NL consistently outperformed free CBD, achieving greater tumor regression, neuronal preservation, and more pronounced biochemical and transcriptional changes.
Conclusion: Encapsulation of CBD into BBB-permeable liposomes enhanced its antitumor, pro-apoptotic, antioxidant, and anti-inflammatory effects in an orthotopic GBM model. CBD-NL demonstrated superior efficacy over free CBD, highlighting liposomal delivery as a promising strategy to improve molecular-targeted therapies for GBM.