Hyaluronic acid (HA) is a naturally occurring mucopolysaccharide that exhibits specific interactions with overexpressed receptors on cancer cells, including CD44, RHAMM, and LYVE-1, facilitating targeted drug delivery to tumors. The present study aims to develop an activated nanostructured lipid carrier (NLC) functionalized with HA as a ligand to improve the selectivity and safety of parenterally administered vinorelbine (Vn). The findings indicate that HA-functionalized NLCs effectively enhanced the selective targeting and accumulation of vinorelbine within tumor tissue, prolonging its retention time and potentiating its cytotoxic effects. Additionally, the observed increase in mice body weight suggests an improved safety profile of the formulation