Hypothesis: Synthetic sugar alcohol mono-behenates with high melting points, surface activity and resistance to enzymatic lipolysis, are expected to form stable single-component solid lipid nanocarriers (SC-SLNs). The preparation methods and the polar head group of the molecules should affect the size and drug encapsulation efficiency. Experiments: SC-SLNs of sugar alcohol mono-behenates with varied polar heads were prepared using emulsification-diffusion method and melting-probe sonication method. Model lipophilic drug fenofibrate was formulated into nanocarriers. The drug release was assessed using the lipolysis model. The structure and drug distribution of the nanocarriers were studied using AFM and TEM. Findings: Both the polar head group of the molecules and the preparation methods affect the particle size and size distribution. Nanocarriers prepared with sorbitol mono-behenates showed the smallest mean size (similar to 100 nm with PdI of 0.26). In addition, they displayed high entrapment efficiency of fenofibrate (95%) and long term drug release. Nanocarriers prepared by emulsification-diffusion method entrapped fenofibrate into lipid bilayers. In contrast, Nanocarriers prepared by melting-probe sonication method had a micelle structure with fenofibrate incorporated into a lipid monolayer. This study provides an insight into the systematic development of novel amphiphilic lipids for solid lipid-based drug delivery system. (C) 2017 Elsevier Inc. All rights reserved.