Lipid-based nanoparticles as drug delivery system for paclitaxel in breast cancer treatment

Paclitaxel (PTX) is a well-known antitumor drug, widely utilized in the treatment of breast, ovarian, head, and neck tumors, among others. The low aqueous solubility (<1.0 mu g/mL; log P = 3.96) limits its use by intravenous route, and alternatives found for the marketed products are associated with high toxicity. Incorporation of PTX into lipid nanocarriers has been considered an interesting nontoxic alternative for this route, but drug loading is usually low. This study aimed to analyze the influence of the lipid composition and three different lipid nanosystems-solid lipid nanoparticles, nanostructured lipid carriers (NLCs), and nanoemulsion-in PTX encapsulation and its biological response. The three proposed systems were prepared by hot melt homogenization followed by ultrasonication. Among the blank formulations first prepared, NLC had the smallest size (74 +/- 1 nm), with negative zeta potential (-11.4 +/- 0.1 mV). The incorporation of 0.10mg/mL PTX into this NLC formulation yielded high and stable encapsulation (0.089 +/- 0.003 mg/mL), also supported by polarized light microscopy and differential scanning calorimetry curves. NLC-PTX was very effective against MCF-7 (IC50 25.33 +/- 3.17 nM) and MDAMB-231 breast cancer cell lines (IC50 2.13 +/- 0.21 nM), compared to free PTX (IC50 > 500 nM). In addition, no significant cytotoxicity was found against fibroblast cells. Taken together, these results demonstrated that PTX was successfully incorporated into NLC with appropriate physicochemical characteristics for intravenous administration, suggesting that the use of NLC as vehicle to incorporate PTX may be a promising strategy in the treatment of breast cancer.