Hyaluronic acid-coated magnetic solid lipid nanoparticles for cancer-targeted delivery of gemcitabine and imaging agent

• Hyaluronic acid-coated magnetic solid lipid nanoparticles (HA/Gem-Mag-SLNs) have been successfully synthesized and characterized for the cancer-targeted delivery of therapeutic and imaging agents, specifically gemcitabine and superparamagnetic iron oxide nanoparticles. • We employed the definitive screening design, a design of experiments approach, to optimize the Gem-Mag-SLN formulation. • The HA/Gem-Mag-SLNs exhibited a slow and sustained release profile, during which about 18 % of Gem was released after 72 h. Hyaluronic acid-coated magnetic solid lipid nanoparticles were formulated for targeted delivery of gemcitabine (Gem) and imaging agents. For this purpose, gemcitabine and superparamagnetic iron oxide nanoparticles (SPIONs) were encapsulated within solid lipid nanoparticles (Gem-Mag-SLNs) and optimized by a definitive screening design (DSD). Then, optimized Gem-Mag-SLNs were coated with hyaluronic acid (HA/Gem-Mag-SLNs) for targeted delivery to tumor cells overexpressing CD44. The physicochemical characterization of prepared nanoparticles was performed by dynamic light scattering (DLS), zeta potential analysis, determination of drug entrapment efficiency (EE), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), transmission electron microscopy (TEM) and vibrating sample magnetometer (VSM). The HA/Gem-Mag-SLNs exhibited a particle size of 133.8 ± 7.3 nm, a negative zeta potential of -71.4 ± 0.3 mV, and an EE of 20.02 ± 2.31 %. Furthermore, magnetic measurements confirmed the superparamagnetic behavior of the HA/Gem-Mag-SLNs. The in vitro release studies of Gem from HA/Gem-Mag-SLNs indicated a slow and sustained release profile. The HA/Gem-Mag-SLNs demonstrated greater potency in inhibiting the growth of MDA-MB-231 cancer cells compared to Gem-Mag-SLNs and free Gem, showing improved targetability to tumor cells. Therefore, our results indicate the potential of the HA/Gem-Mag-SLNs as suitable nanoplatforms for cancer-targeted therapy and imaging.