Preparation and Cytopharmacology Evaluation of Self-Assembled Saikosaponin D-Cannabidiol Nanoparticles
This study reports the fabrication and in vitro evaluation of carrier-free self-assembled nanoparticles (SSD-CBD) composed of saikosaponin D (SSD) and cannabidiol (CBD) at a 3:1 mass ratio via nano co-precipitation. Assembly mechanisms were probed using XPS, FTIR, and 1H-1H NOESY, revealing hydrogen bonding and hydrophobic interactions as principal driving forces. Physicochemical characterization by TEM and DLS confirmed a stable nanoscale architecture. The formulation exhibited pH-responsive release, preferentially discharging payload in tumor microenvironment (pH 6.8) while retaining stability at physiological pH 7.4. In HepG2 hepatocellular carcinoma cells, SSD and CBD displayed synergy with a combination index (CI) of 0.79. MTT assays, Annexin V-FITC/PI flow cytometry, and caspase activity measurements demonstrated that SSD-CBD nanoparticles induce apoptosis via the mitochondrial pathway. The carrier-free strategy addresses CBD's poor aqueous solubility and instability, simultaneously improving delivery efficiency and enabling precise synergistic drug co-administration. These findings provide an experimental foundation for intelligent nanomedicine development based on SSD. However, in vivo pharmacokinetics, tissue distribution, tumor accumulation, and potential hepatotoxicity of SSD in nanoformulation remain unresolved. Future work should focus on surface engineering (e.g., PEGylation or targeting ligand modification) to enhance stability and tumor targeting, integration of immunomodulatory components, and scalable GMP-compliant manufacturing with comprehensive quality control.