Co-Encapsulation of Cannabinoids and Paclitaxel in Lipid Nanoparticles: Characterization and Cytotoxic Evaluation in Breast Cancer Cells

Breast cancer (BC) is the most common malignant neoplasm among women and a major global public health problem. Chemotherapy remains the cornerstone of BC treatment, primarily using taxanes and anthracyclines. However, the toxicity of these therapies and their severe side effects pose major challenges. Paclitaxel (PTX) is an important chemotherapeutic agent used in BC treatment; however, its clinical application is limited by low water solubility. Cannabigerol (CBG), a non-psychoactive phytocannabinoid, has antitumor potential, but presents limitations related to stability, bioavailability, and low water solubility. In this context, nanostructured lipid carriers (NLCs) represent a promising strategy for improving the delivery and therapeutic performance of these compounds. Therefore, the aim of this study was to develop an NLC formulation combining PTX and CBG to promote sustained release and improve their delivery for future application in BC treatment. Additionally, tocopherol acetate (0.1%) was incorporated into the formulation as an antioxidant. The formulations were obtained by emulsification followed by ultrasonication and optimized using experimental design. The formulation developed (NLC-CBG-PTX), during the 7 months of stability, showed, by DLS, an average particle size of approximately 180 nm, homogeneous particle distribution (PDI < 0.2), negative zeta potential (-32.1 mV), and approximately 3 × 10¹³ particles/mL, as determined by NTA. The formulation showed high encapsulation efficiency (>99%) for both PTX and CBG and spherical morphology, as revealed by TEM. X-ray diffraction (XRD) analysis indicated the formation of a lipid matrix with low crystallinity, favoring compound incorporation. The formulation maintained physicochemical stability for up to 190 days at 25 °C, preserving particle size, PDI, and zeta potential, as well as high chemical stability during storage. In vitro release studies conducted over 24 h demonstrated a sustained-release profile for both encapsulated compounds, whereas the free compounds were almost completely released within 5 h. The release curves of the encapsulated actives were best fitted by the Weibull model (R² = 0.9998 for PTX and R² = 0.9980 for CBG). Cell viability assays are under course to evaluate the cytotoxic activity of the formulation in BC models.

This work was supported by CNPq (PIBITI) and by FAPESP (# 2025/01405-1. 2024/02479-6).