Unraveling the role of hyaluronic acid on the targeting of vinorelbine-loaded NLC for lung cancer
Hyaluronic acid (HA) is a naturally occurring mucopolysaccharide that interacts specifically with overexpressed receptors on cancer cells,such as CD44, RHAMM, and LYVE-1, enabling targeted drug delivery to tumors. The present work aims to prepare an activated nanolipidcarrier (NLC) using HA as a ligand to enhance the selectivity and safety of parenterally administered vinorelbine (Vn). The preparationmethod included the chemical conjugation of pegylated-DSPE with HA, followed by the loading of Vn using ultrasonication-homoge-nization to prepare activated HA-NLC (Vn-loaded HA-NLC). In vitro evaluation for the prepared formulation had a mean particle sizeof 102 nm, a zeta potential of -44.1 mV, and gave a drug release of 85.23% within 48 hours with an IC50 of 35.7 μg/mL against the lungcancer cell line A549 in comparison to the marketed drug and non-activated Vn-loaded NLC, which gave IC50 values of 45.65 μg/mL and57.29 μg/mL, respectively. The in vivo study in mice of the Kunming strain included the induction of lung cancer (LL2) xenograft (equiv-alent to humanized A549), measurement of mice body weight and tumor volume, histopathological study for 4 weeks, and MRI follow-upscan of tumor tissue for 24 hours using SPION as a contrast agent. The result showed a significant (P < 0.05) increase in body weight, exten-sive tumor apoptosis, smaller tumor size, and better accumulation inside tumor tissue for mice treated with activated HA-NLC comparedto non-activated NLC and marketed products. It was concluded that HA-NLC promoted the selective targeting and accumulation of Vn in-side tumor tissue, prolonging the retention duration and enhancing the drug’s cytotoxic effect with increased mice weight as a sign of safety.