Co-delivery of Paclitaxel and Cannabidiol in Lipid Nanoparticles Enhances Cytotoxicity Against Melanoma Cells

Abstract

Although chemotherapy regimens are well-established in clinical practice, chemoresistance and adverse side effects pose significant obstacles in cancer treatment. Paclitaxel (PTX), a widely used chemotherapeutic agent, faces formulation challenges due to its poor solubility and permeability. Research suggests that the phytochemical Cannabidiol (CBD) holds potential not only in targeting cancer cells but also in alleviating pain and nausea, thereby improving the quality of life for cancer patients. However, CBDs clinical application is also limited by its poor solubility, low bioavailability, and susceptibility to oxidation. Nanostructured lipid carriers (NLCs) represent a promising drug delivery system for hydrophobic compounds like PTX and CBD and allows their co-encapsulation. Nonetheless, achieving a stable formulation requires identifying suitable preparation methods and excipients. The aim of this study was to develop and optimize an NLC formulation for the co-encapsulation of PTX and CBD. Using factorial design, an optimized formulation was obtained with homogeneous particle sizes (200 nm), negative zeta potentials (-17 mV), particle concentration of 1013 particles/mL, spherical morphology (TEM images), and a lipid core with low crystallinity (as confirmed by XRD). To evaluate the therapeutic potential of the drug combination, cell viability assays were conducted on murine melanoma cells (B16-F10) at different exposure times (24 and 48 hours). The NLC-CBD-PTX formulation significantly reduced cell viability in a time- and concentration-dependent manner, demonstrating at least 75% greater activity at 24 hours compared to each drug individually whether free (PTX, CBD) or encapsulated (NLC-PTX, NLC-CBD). This indicates a synergistic effect of the encapsulated drugs on cytotoxicity. In conclusion, an innovative pharmaceutical formulation co-encapsulating PTX and CBD was validated, showing potential to enhance antitumor efficacy, overcome chemoresistance, reduce side effects, and broaden therapeutic applications. The resulting NLCs exhibited favorable physicochemical properties, supporting their suitability for various routes of administration.