Preparation and characterization of PBS (Polybutylene Succinate) nanoparticles containing cannabidiol (CBD) for anticancer application

Cannabidiol (CBD), a major constituent of Cannabis sativa, has demonstrated a broad range of therapeutic properties in human studies. Notably, CBD has shown anticancer activity in preclinical cancer models. However, its low water solubility poses challenges for bioavailability, necessitating the development of drug delivery systems to enhance its efficacy. This study aimed to create CBD-loaded Poly (butylene succinate) (PBS) nanoparticles and evaluate their effectiveness in in vitro cancer models. The nanoparticles, with an average size of 175 nm, were produced using a modified double emulsion/solvent evaporation technique. The release profile of CBD from the nanoparticles exhibited an initial rapid release followed by a slower sustained release. Cytotoxicity assays demonstrated that the CBD-PBS nanoparticles retained the anticancer effects of free CBD, selectively reducing the viability of cancer cell lines without affecting non-transformed fibroblasts. Additionally, the nanoformulation modulated key cellular pathways, as indicated by decreased AKT phosphorylation and increased LC3-II levels, suggesting that the encapsulated CBD preserved its ability to induce autophagy-mediated cell death in cancer cells. The nanoformulation also effectively inhibited cell migration in highly invasive prostate cancer cells, mirroring the effects of free CBD, while not impacting the migration of non-tumoral fibroblasts. These results underscore the therapeutic potential of this CBD nanoformulation, setting the stage for further in vivo investigations.