Structure Analysis of Solid Lipid Nanoparticles for Drug Delivery: A Combined USANS/SANS Study

Abstract Suspensions of solid lipid nanoparticles (SLNs) stabilized with emulsifiers have been extensively investigated (since the 1990s) as drug carriers, although details of their ultrastructure are poorly defined. Previously, a novel microwave‐assisted microemulsion‐based technique to prepare SLNs was reported. To understand the detailed internal structure of these SLNs, ultra‐small angle neutron scattering (USANS) and small angle neutron scattering (SANS) experiments are conducted on suspensions of hydrogenated stearic acid SLNs stabilized with hydrogenated Tween 20 surfactant in D₂O. Together, SANS and USANS gives a combined Q range of 0.000047 to 0.6 Å⁻¹ (corresponding to a size range of ≈1 nm–15 µm). This extended Q range allows a comprehensive understanding of the hierarchical structure of SLNs. The data are consistent with the multi‐length scale structure of SLNs having polydispersed large particles with roughened surfaces at the microscale level. At the nanoscale level, the results are consistent with the SLNs having an ellipsoidal shape intermediate between spheres and rods, with a crossover from mass fractals to surface fractals. The elucidation of this structure is particularly important given that the structure influences the stability and drug release properties of the nanoparticles. These results assist in the development of systems with desired shape and properties.