Abstract: OBJECTIVE To prepare the solid lipid nanoparticles(SLN) via supercritical assisted atomization(SAA) and investigate the effect of formulation and process on physicochemical characteristics of nanoparticles (NPs). METHODS With self-made SAA particle-producing equipment, stearic acid(SA) based SLN was produced, and the effect of SA concentration, flow ratio of supercritical CO₂ and material solution, pore size of nozzle, on particle size of SLN were investigated to discover the appropriate process conditions. SLN loading insulin, a hydrophilic macromolecule drug, was produced and their physicochemical characteristics was observed, such as size, zeta-potential, entrapment efficiency(EE) and drug-loading ratio(DL). RESULTS Particle size of NPs was depended on material concentration, flow ratio of supercritical CO₂ and material solution, pore size of nozzle. SLN with mean size <300 nm were obtained through formulation and process adjustment during preparation. Insulin-loaded SLN with mean size of about 300 nm, EE 72.2% and DL 3.44% was obtained, which released drug slowly during 12 h in vitro. Poloxamer-modified formulation made SLN with reduced size and distribution range, meanwhile the drug EE was decreased and burst-release was significant. CONCLUSION SAA is successfully applied to produce SLN and hydrophilic-drug-loaded SLN with modified releasing profile.