ASSOCIATION OF PACLITAXEL AND CANNABIDIOL IN NLC: FORMULATION DEVELOPMENT AND IN VITRO TESTS

Paclitaxel (PTX) is a broad-spectrum chemotherapeutic agent, highly hydrophobic, belonging to the taxane class and showing neuropathy as one of its side effects. Cannabidiol (CBD), a lipophilic endocannabinoid has been studied for its potential applications in chronic pain, inflammation, and cancer. Nanostructured lipid carriers (NLC) are drug-delivery systems of long-term stability that have the ability to encapsulate hydrophobic drugs within their lipid matrix, preventing premature drug release and providing aqueous formulations that can be intravenously administered. Therefore, the objective of this study was to combine PTX and CBD in a NLC formulation of improved anticancer properties and reduced side effects. Factorial design was used for the optimization of the NLC-PTX-CBD formulation (lower sizes/PDI, and higher zeta potentials), and stability was assessed over a period of 60 days. Afterwards, the optimized formulation was tested in vitro on a melanoma cell line (B16-F10). The optimized formulation showed by DLS, a homogeneous distribution of particles (PDI = 0.2) with average size of 200 nm, negative zeta potential (-17 mV), ca 4 x 1013 particles/mL (as determined by NTA) and spherical morphology (TEM images). To clarify the effect of CBD, a control NLC formulation (referred to as NLC-PTX-MIG) was prepared using Miglyol® as the liquid lipid, instead of CBD. Cell viability of B16-F10 cells was evaluated at different times (24 and 48 h), after treatment with commercial PTX (Taxol®), the optimized formulation (NLC-PTX-CBD) and the control formulation (NLC-PTX-MIG). When treated for 24 h at the highest concentration of 2 mM of PTX, cell viability was reduced to 21.4 ± 2.2% with Taxol®, 20.0 ± 0.8% with NLC-PTX-CBD and 39.5 ± 4.3% with NLC-PTX-MIG. After 48 h, cell viability further decreased to 10.0 ± 2.1% with Taxol®, 9.7 ± 0.8% with NLC-PTX-CBD and 15.6 ± 2.0% with NLC-PTX-MIG. Thus, in this cancer cell line the NLC-PTX-CBD formulation significantly reduced (p < 0.05) cell viability in a time and concentration-dependent manner, compared to the reference Taxol® and NLC-PTX-MIG. In conclusion, a new technology-based pharmaceutical formulation for chemotherapy, combining PTX and CBD, was prepared and tested in vitro, demonstrating increased cytotoxic potential against melanoma cells. Therefore, this formulation shows promising properties for further in vivo testing, with potential improvements not only in its antitumor effect but also in reducing systemic and neuropathic toxicity due to its association with cannabidiol.