To investigate the potential of modified solid lipid nanoparticles (SLN) for the delivery of paclitaxel (PAX).SLN loaded with PAX were prepared via modified high-pressure hot homogenization. Formulation parameters were optimized to obtain a high-quality delivery system. SLN cores were coated, layer-by-layer, with a chitosan and hyaluronan (HA) shell. Selectivity toward HA receptors was tested in a breast cancer cell line, MCF-7.Stable and reproducible nano-sized and negatively charged nanoparticles resulted. Findings reveal that chitosan-HA-coated SLN facilitated the targeting, cellular uptake and the time-/dose-controlled delivery and release of PAX, enhancing intrinsic chemotherapeutic activities.SLN are suitable carrier candidates for nano-oncology given their localized, and potent cytotoxic potential overcoming multidrug-resistant cancer cells.