DEVELOPMENT OF BETA-CARYOPHYLLENE-FUNCTIONALIZED LIPID NANOPARTICLES CONTAINING PACLITAXEL FOR THE TREATMENT OF BREAST CANCER

Breast cancer (BC) is the most common and frequently metastatic malignant tumor in women, with a steadily increasing incidence worldwide. Chemotherapy regimens based on taxanes and anthracyclines remain the cornerstone of BC clinical treatment. However, these strategies lack targeted therapeutic action and exhibit significant variability in response and prognosis. Drug delivery systems hold promise for enhancing the efficacy of chemotherapy by promoting sustained release and reducing systemic toxicity. In here, we developed nanostructured lipid carriers (NLC) containing β-caryophyllene (BCP), a functional excipient with anticancer and analgesic properties, and paclitaxel (PTX) to enhance the therapeutic efficacy of conventional chemotherapy. The NLC-BCP-PTX formulation was optimized by Design of Experiments and kept, during 7 months of stability, a monodisperse population (PDI < 0.2) of particles of ca. 200 nm in size, negative Zeta potential (-30.6 mV), ca. 2.7x10¹³ particles/mL and spherical morphology. The formulation exhibited high encapsulation efficiency (99%) for both PTX and BCP. Structural organization details were provided by Differential scanning calorimetry and X-ray diffraction. In vitro evaluations of the formulation's effects on cell viability were conducted using normal fibroblasts (NIH-3T3, ATCC CRL-1658TM). A control formulation prepared without BCP and its control (NLC-PTX and NLC-CTL) exhibited no toxicity to the cells. Pure BCP was also non-toxic, but when encapsulated (NLC-BCP) cytotoxicity was observed at concentrations exceeding 10¹⁰ particles/mL (IC₅₀ = 2.2 x 10¹¹ particles/mL). The NLC-BCP-PTX formulation reduced cell viability at concentrations greater than 5 mM and was found to be significantly more cytotoxic (p<0.0001) than the commercially available PTX formulation, Taxol^® (IC₅₀ = 0.02 and 0.23 mM, respectively). Ongoing trials aim to access its effect over tumor cell lines (4T1 and MCF-7). Future in vivo studies will compare the anti-tumor effect of NLC-BCP-PTX with those of Taxol^® to potentially improve prognosis and quality of life for BC patients.