Abstract: AimTo investigate the cellular uptake of monostearin solid lipid nanoparticles (MSLN) and the influence on the cellular uptake by MSLN modified with PEG2000 in human-type II cell alveolar epithelial cell line (A549) and murine macrophages cell line (J774A1). MethodsMSLN were prepared by a novel solvent diffusion method. The particle size distribution and zeta potential of MSLN, measured by light scattering and electrophoretic mobility, were investigated. The cytotoxicity of MSLN and MTX-loaded MSLN in A549 cells were performed by the MTT method. Rhodamine B was incorporated into solid lipid nanoparticles as fluorescent marker, after PEG2000 integrating monostearin during preparation, the cellular uptake of MSLN by A549 and J774A1 cell lines were determined spectrofluorimetrically. ResultsThe IC₅₀ of MSLN and MTX-loaded MSLN on A549 cells were 227.56 μg·mL^-1 and 71.37 μg·mL^-1, respectively. The percentage of cellular uptake showed a negative correlation to the concentration of MSLN in incubation medium and the internalization behaved rapidly. Contrary to situation in J774A1 cell line, internalization of solid lipid nanoparticles was promoted with increasing the content of PEG2000 incorporated into MSLN in A549 cell line. ConclusionAfter modifying MSLN with PEG2000, it represents relative lower phagocytosis by J774A1 cell line and higher uptake in A549 cell line.