Development and characterization of DHA-integrated nanostructured lipid carrier formulations for enhanced cellular binding and uptake

In the present study, the effect of the variations in lipid and emulsifier composition of nanostructured lipid carriers (NLCs) designed for drug delivery on cancer treatment, related with their physicochemical properties and cellular interactions, was explored. Stearic acid was used as the solid lipid matrix, combined with either oleic acid or docosahexaenoic acid (DHA) as the liquid lipid. The resulting NLCs were characterized using dynamic light scattering, atomic force microscopy, and differential scanning calorimetry, revealing uniform dispersion and particle size within the 100–200 nm range which is suitable for overcoming biological barriers. Cellular studies were performed using R18-labeled NLCs on ECV304 (carcinoma) and U87 (glioblastoma) cell lines to assess cytotoxicity and uptake. No significant toxicity was observed up to 5 µg/mL. Among the formulations, NLCs containing DHA (NLC-4_DHA) demonstrated markedly enhanced cellular binding and uptake, particularly in ECV304 cells, as confirmed by flow cytometry analysis. These findings indicate that DHA-based NLCs possess favorable biocompatibility and interaction profiles, positioning them as promising candidates for targeted drug delivery in cancer therapy.