Optimization and in vitro/in vivo performance of paclitaxel-loaded nanostructured lipid carriers for breast cancer treatment

Despite the wide use of paclitaxel (PTX) as antitumor drug, its intravenous administration is still limited by the low aqueous solubility ( < 1.0 mu g/mL; log P = 3.96). Taxol (R) is the main commercial PTX-based product, but the high concentration of surfactant and ethanol necessary for PTX solubilization is usually associated with severe toxic effects. The incorporation of PTX into lipid nanocarriers has been considered an interesting nontoxic alternative to Taxol (R), however, the drug loading is usually low. Thus, our main goal was to incorporate PTX in nanostructured lipid carriers (NLC) with high encapsulation efficiency and suitable characteristics for the evaluation of in vitro and in vivo biological responses. The optimized NLC formulation presented average size of 213 +/- 9 nm, negative zeta potential ( - 18 +/- 3 mV) and high encapsulation (0.9 mg/mL), as confirmed by FTIR and XRD analyses. The in vitro cytotoxic and anti-clonogenic effects of NLC-PTX against MDA-MB-231 cells were significantly higher than free PTX, and no significant cytotoxicity was found against L929 fibroblast cells. Radiolabeling of NLC-PTX with Tc-99m was successfully attained (over 90% radiopurity) and stable in saline and mice plasma. The Tc-99m-NLC-PTX showed a tumor accumulation 1.5- and 1.7-fold higher than the Tc-99m-PTX dispersion in tumor-bearing mice after 30 and 120 min of post-administration, respectively. Therefore, PTX was successfully incorporated into NLC, with physicochemical characteristics suitable for intravenous administration, and with suggestive collaborative use in new strategies for the treatment of breast cancer.